Low-risk Individuals Research Articles

The Benefits of Hindsight and Modern Risk Assessment Tools: An Evaluation of Minnesota’s COVID-19 Early Release Program

Given the devastating effects of COVID-19 on congregate living settings, many correctional agencies have been forced to expedite the release of incarcerated persons beginning in 2020. This research evaluated the recidivism outcomes of 158 individuals released early from prison in response to the pandemic compared to a similar cohort of standard releases. Cox regression analyses revealed that individuals released early were no more or less likely to be re-arrested or returned to prison for a supervision violation compared to the control sample, but they were significantly less likely to be convicted of a new offense. This research demonstrated that carefully selected low-risk individuals can be released early from prison without compromising public safety.

The m7G-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Tumour Immune Infiltration in Colon Cancer.

With high morbidity and mortality, colon cancer (CC) is considered as one of the most often diagnosed cancers around the world. M7G-related lncRNA may provide a regulatory function in the formation of CC, but the principle of regulation is still unclear. The purpose of this research was to establish a novel signature that may be used to predict survival and tumour immunity in CC patients. Data about CC in TCGA was collected for analysis, coexpression analysis and univariate Cox analysis were used to screen prognostic m7G-related lncRNAs. A consensus clustering analysis based on prognostic m7G-related lncRNAs was applied, and a prognosis model based on least absolute shrinkage and selection operator (LASSO) regression analysis was established. Independent prognostic analysis, nomogram, PCA, clinicopathological correlation analysis, TMB, survival analysis, immune correlation analysis, qRT–PCR and clinical therapeutic compound prediction were also applied. 90 prognostic m7G-related lncRNAs were found, GO and KEGG analysis showed that prognostic m7G-related lncRNAs were mainly related to cell transcription and translation. The results of the consensus clustering analysis revealed substantial disparities in survival prognosis and tumour immune infiltration between two clusters. We built a risk model with 21 signature m7G-related lncRNAs, patients in the high-risk group had a considerably poorer prognosis than those in the low-risk group. Independent prognostic analysis confirmed that patients’ prognosis was linked to their tumour stage and risk score. PCA, subgroups with distinct clinicopathological characteristics were studied for survival, multi-index ROC curve, c-index curve, the survival analysis of TMB, and model comparison tested the reliability of risk model. A tumour immunoassay revealed a substantial difference in immune infiltration between high-risk and low-risk individuals. Five chemicals were eliminated, and qRT–PCR indicated that the four lncRNAs were expressed differently. Overall, m7G-related lncRNA is closely related to colon cancer and the 21 signature lncRNAs risk model can efficiently evaluate the prognosis of CC patients, which has a possible positive consequence for the future diagnosis and therapy of CC.

Clinical risk, sociodemographic factors, and SARS-CoV-2 infection over time in Ontario, Canada

We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction < 0.0001). Prior to the first-wave peak, SARS-CoV-2 infection increased with age whereas this association reversed thereafter. Risk factors that persisted included male sex, residing in lower income neighborhoods, residing in more racially/ethnically diverse communities, immigration to Canada, hypertension, and diabetes. While there was a reduction in infection rates after mid-April 2020, there was less impact in regions with higher racial/ethnic diversity. Immediately following the initial peak, individuals living in the most racially/ethnically diverse communities with 2, 3, or ≥ 4 risk factors had ORs of 1.89, 3.07, and 4.73-fold higher for SARS-CoV-2 infection compared to lower risk individuals in their community (all P < 0.0001). In the latter half of 2020, this disparity persisted with corresponding ORs of 1.66, 2.48, and 3.70-fold higher, respectively. In the least racially/ethnically diverse communities, there was little/no gradient in infection rates across risk strata. Further efforts are necessary to reduce the risk of SARS-CoV-2 infection among the highest risk individuals residing in the most racially/ethnically diverse communities.

Cardiac Complications of COVID-19 in Low-Risk Patients.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in over 6 million deaths and significant morbidity across the globe. Alongside common respiratory symptoms, COVID-19 is associated with a variety of cardiovascular complications in the acute and post-acute phases of infection. The suggested pathophysiological mechanisms that underlie these complications include direct viral infection of the myocardium via the angiotensin-converting enzyme 2 (ACE2) protein and a cytokine release syndrome that results in indirect inflammatory damage to the heart. Patients with pre-existing cardiovascular disease and co-morbidities are generally more susceptible to the cardiac manifestations of COVID-19. However, studies have identified a variety of complications in low-risk individuals, including young adults and children. Myocarditis and paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS) are among the adverse events reported in the acute phase of infection. Furthermore, patients have reported cardiac symptoms persisting beyond the acute phase in post-COVID syndrome. This review summarises the acute and chronic cardiac consequences of COVID-19 in low-risk patients, explores the pathophysiology behind them, and discusses new predictive factors for poor outcomes.

ASSOCIATION OF INTER-ARM SYSTOLIC BLOOD PRESSURE DIFFERENCES WITH ARTERIOSCLEROSIS AND ATHEROSCLEROSIS: A COHORT STUDY OF 117,407 PEOPLE

Objective: Inter-arm blood pressure differences (IADs) are known to be associated with adverse cardiovascular outcomes. We evaluated the distribution of IADs in a large cohort of apparently healthy people and the association of IADs with brachial-ankle pulse wave velocity (baPWV) and coronary artery calcium (CAC). Methods: Blood pressure was measured in both arms of 117,407 people who participated in the Kangbuk Samsung Health Study. IAD was defined as the absolute difference in systolic blood pressure in both arms and was confirmed by measuring the baPWV using an automatic oscillometric device. Arterial stiffness was measured by the baPWV, and CAC was assessed using multi-detector computed tomography. Design and method: Blood pressure was measured in both arms of 117,407 people who participated in the Kangbuk Samsung Health Study. IAD was defined as the absolute difference in systolic blood pressure in both arms and was confirmed by measuring the baPWV using an automatic oscillometric device. Arterial stiffness was measured by the baPWV, and CAC was assessed using multi-detector computed tomography. Results: The mean IAD in the overall subjects was 3.09 ± 2.83 mmHg, 6 mmHg in the 90th percentile, 8 mmHg in the 95th percentile, and 10 mmHg in the 97th percentile. In the multivariable-adjusted analysis of 92,949 subjects excluding those with a history of HTN, DM, and cardiovascular disease (CVD), increasing IAD did not statistically increase the risk of developing a CAC &gt; 0. However, IAD was associated with a baPWV of &gt; 1,400 cm/s (odds ratio [95% confidence interval], 1.23 [1.13–1.35] in the total cohort, 1.19 [1.08–1.31] in males, and 1.39 [1.11–1.73] in females). Conclusions: More than 97% of all participants had an IAD of 10 mmHg or less. IAD was significantly associated with arterial stiffness, reflecting arteriosclerosis, but not the presence of CAC, reflecting atherosclerosis. IAD may be a valuable tool for the early detection of asymptomatic, low-risk individuals with subclinical arterial disease.

Clostridioides difficile infection in a rural New Zealand secondary care centre: an incidence case-control study.

Clostridioides difficile infection (CDI) is a form of antibiotic-associated infectious diarrhoea resulting in significant morbidity and mortality. Community-acquired disease in low-risk individuals is increasingly recognised. There are limited New Zealand data published. To determine the incidence and location of onset of CDI cases in the Manawatu region, and further describe the demographics, risk factors and prevalent C. difficile ribotypes of the population. We performed an incidence case-control study of CDI in the Manawatu region between September 2018 and September 2019. Cases were matched to controls with a negative test for C. difficile. Demographic and comorbidity data, location of onset, drug exposure, disease recurrence and 30-day mortality were collected. Ribotype analysis was performed on C. difficile isolates. Thirty-two specimens tested toxin positive over 12 months, yielding an incidence of 18.3 cases per 100 000 person-years. Twenty-five percent of cases had community onset disease. Cases were more likely to have had amoxicillin/clavulanate or ceftriaxone prescribed. Elevated blood white cell count and lower HbA1c were significantly associated with CDI. The dominant ribotype was 014/020. Two cases were RT 023. Our data are similar to previous national data. RT 023 has not been previously reported in New Zealand and has been associated with severe colitis. We demonstrated a significant proportion of community-acquired cases and the true incidence might be higher. Vigilance for community onset disease is required. These data may allow observation of temporal changes in incidence and infection patterns of CDI in New Zealand.

Transcatheter Aortic Bioprosthesis Durability: A Single-Center Experience

BackgroundTranscatheter aortic valve implant (TAVI) is gaining momentum in the treatment of severe, symptomatic aortic valve stenosis, and its indication is expanding to lower surgical risk individuals, who are generally younger and have a long life expectancy. Therefore, transcatheter bioprostheses durability appears of critical importance. Aim of the present study is to evaluate mid-term outcomes of TAVI in a high-volume single center cohort. MethodsWe analyzed all consecutive patients (n = 408) who underwent transfemoral TAVI at a single, high-volume center, between 2007 and 2014. Study objectives were all-cause death and bioprosthetic valve failure (BVF) at long term follow-up. Structural valve deterioration (SVD), BVF and valve-related death were defined according to current international standards. Follow-up was performed by in person visit and transthoracic echocardiography, which was obtained only in a minority of patients, or phone call as per patient preference. ResultsAt a median follow-up of 1821 days, overall mortality was 64.5%, with cardiovascular disease accounting for roughly half of total deaths. Valve-related deaths occurred in 10 patients. Seventeen patients were diagnosed with BVF, and 15 required repeat intervention. Moderate and severe SVD were observed in 10 and 7 patients, respectively. In the subgroup of patients with echocardiographic mid-term follow-up (n = 76), no significant increase of transprosthetic gradients nor increase of significant regurgitation was detected. ConclusionIn the present unselected, all-comers cohort, TAVI bioprostheses appeared to have excellent durability at long-term follow-up.

Role of antibiotic prophylaxis on surgical site infection prevention in a low-risk population undergoing laparoscopic cholecystectomy: A randomized controlled study

ObjectiveTo compare the incidence of surgical site infections (SSIs) in low-risk patients undergoing laparoscopic cholecystectomy (LC) with pre-operative antibiotics versus no pre-operative antibiotics administration. Study designRandomized controlled study. SettingHepatobiliary department, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Pakistan, from Jul 1, 2018, to Jun 30, 2021. MethodsThis is a prospective, open-label, randomized study. Individuals scheduled for laparoscopic cholecystectomy who met the inclusion requirements were randomly assigned to two groups. Group A patients received pre-operative antibiotics (intravenous cefazolin 2-g), and group B patients were operated on without administration of pre-operative antibiotics. Post-operatively, patients were studied for the occurrence of SSIs for 30 days. ResultsThe mean age of patients in group A was 40.6 + 5.2 years, while group B was 41.04 + 5.03. The male to female ratio was 1:3. Gender distribution showed female dominance in both groups, i.e., 78.74% in group A and 76.80% in group B. The incidence of SSI in group A was 3.98%, while in group B was 4.9% (p-value = 0.584). No statistical significance was found while comparing both groups' age, gender, operative duration, and hospital stay. ConclusionThis study showed comparable results between both groups, and prophylactic antibiotics have no impact in preventing SSIs. In low-risk individuals undergoing laparoscopic cholecystectomy, the incidence of SSIs is quite low, and prophylactic antibiotics can be avoided.

Smoking Cessation Counseling in the PreAnesthesia Testing Clinic: A Quality Improvement Initiative

PurposeTo determine the feasibility and effectiveness of an Advanced Practice Provider (APP) led smoking cessation counseling service integrated into the preanesthesia evaluation for adults preparing for an elective procedure who smoke. DesignQuasi experimental study. MethodsAn educational in-service was provided to staff members in the Preanesthesia Testing Clinic prior to the integration of the smoking cessation counseling intervention. Knowledge retention was assessed using a pre- and post-test. After the training was complete, staff members began to identify eligible individuals for smoking cessation counseling. Individuals who met the inclusion criteria were stratified into two groups based on their perioperative risk and medical history. High-risk individuals were counseled immediately by the APP. Low risk individuals were first screened by the Registered Nurse and internally referred to the APP for cessation counseling. Those who received smoking cessation counseling were referred to third party smoking cessation support services for ongoing follow up. FindingsIndividuals stratified into the low-risk group reported smoking significantly less postoperatively after preoperative telephonic smoking cessation counseling. ConclusionThe results demonstrate positive smoking cessation outcomes supporting that it is feasible and advantageous to integrate smoking cessation counseling into the preanesthesia evaluation for adults preparing for an elective procedure.

Morphological Biomarkers in the Amygdala and Hippocampus of Children and Adults at High Familial Risk for Depression.

Major Depressive Disorder (MDD) is highly familial, and the hippocampus and amygdala are important in the pathophysiology of MDD. Whether morphological markers of risk for familial depression are present in the hippocampus or amygdala is unknown. We imaged the brains of 148 individuals, aged 6 to 54 years, who were members of a three-generation family cohort study and who were at either high or low familial risk for MDD. We compared surface morphological features of the hippocampus and amygdala across risk groups and assessed their associations with depression severity. High- compared with low-risk individuals had inward deformations of the head of both hippocampi and the medial surface of the left amygdala. The hippocampus findings persisted in analyses that included only those participants who had never had MDD, suggesting that these are true endophenotypic biomarkers for familial MDD. Posterior extension of the inward deformations was associated with more severe depressive symptoms, suggesting that a greater spatial extent of this biomarker may contribute to the transition from risk to the overt expression of symptoms. Significant associations of these biomarkers with corresponding biomarkers for cortical thickness suggest that these markers are components of a distributed cortico-limbic network of familial vulnerability to MDD.

Colorectal cancer surveillance by colonoscopy in a prospective, population-based long-term Swiss screening study - outcomes, adherence, and costs.

Background The success of colorectal cancer (CRC) screening depends mainly on screening quality, patient adherence to surveillance, and costs. Consequently, it is essential to assess the performance over time. Methods In 2000, a closed cohort study on CRC screening in individuals aged 50 to 80 was initiated in Uri, Switzerland. Participants who chose to undergo colonoscopy were followed over 18 years. We investigated the adherence to recommended surveillance and collected baseline characteristics and colonoscopy data. Risk factors at screening for the development of advanced adenomas were analyzed. Costs for screening and follow-up were evaluated retrospectively. Results 1278 subjects with a screening colonoscopy were included, of which 272 (21.3%; 69.5% men) had adenomas, and 83 (6.5%) had advanced adenomas. Only 59.8% participated in a follow-up colonoscopy, half of them within the recommended time interval. Individuals with advanced adenomas at screening had nearly five times the risk of developing advanced adenomas compared to individuals without adenomas (24.3% vs. 5.0%, OR 4.79 CI 2.30–9.95). Individuals without adenomas developed advanced adenomas in 4.9%, including four cases of CRC; three of them without control colonoscopy. The villous component in adenomas smaller than 10 mm was not an independent risk factor. Costs for screening and follow-up added up to CHF 1’934’521 per 1’000 persons screened, almost half of them for follow-up examinations; 60% of these costs accounted for low-risk individuals. Conclusion Our findings suggest that follow-up of screening colonoscopy should be reconsidered in Switzerland; in particular, long-term adherence is critical. Costs for follow-up could be substantially reduced by adopting less expensive long-term screening methods for low-risk individuals.

Critical weaknesses in shielding strategies for COVID-19.

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has led to a wide range of non-pharmaceutical interventions being implemented around the world to curb transmission. However, the economic and social costs of some of these measures, especially lockdowns, has been high. An alternative and widely discussed public health strategy for the COVID-19 pandemic would have been to 'shield' those most vulnerable to COVID-19 (minimising their contacts with others), while allowing infection to spread among lower risk individuals with the aim of reaching herd immunity. Here we retrospectively explore the effectiveness of this strategy using a stochastic SEIR framework, showing that even under the unrealistic assumption of perfect shielding, hospitals would have been rapidly overwhelmed with many avoidable deaths among lower risk individuals. Crucially, even a small (20%) reduction in the effectiveness of shielding would have likely led to a large increase (>150%) in the number of deaths compared to perfect shielding. Our findings demonstrate that shielding the vulnerable while allowing infections to spread among the wider population would not have been a viable public health strategy for COVID-19 and is unlikely to be effective for future pandemics.

Characterizing HIV-Preventive, Plasma Tenofovir Concentrations-A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis Clinical Trials.

Daily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration. Participant data from TFV-based daily oral and topical active arms of phase 3 trials (iPrEx, VOICE, and Partners PrEP) were pooled (n = 2950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models. Around 50% of the individuals were estimated to be adherent, which differed from self-reported adherence (∼90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high-risk females (45.8 ng/mL) compared with high-risk males (16.1 ng/mL) and to low-risk individuals (∼7.5 ng/mL). Dosing simulations indicated that high-risk women require full adherence to maintain protective levels. Using the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high-risk females need higher levels of plasma TFV to achieve HIV protection compared with males. HIV protection exceeds 90% in all populations if daily adherence is achieved.

Unselected Population Genetic Testing for Personalised Ovarian Cancer Risk Prediction: A Qualitative Study Using Semi-Structured Interviews.

Unselected population-based personalised ovarian cancer (OC) risk assessments combining genetic, epidemiological and hormonal data have not previously been undertaken. We aimed to understand the attitudes, experiences and impact on the emotional well-being of women from the general population who underwent unselected population genetic testing (PGT) for personalised OC risk prediction and who received low-risk (<5% lifetime risk) results. This qualitative study was set within recruitment to a pilot PGT study using an OC risk tool and telephone helpline. OC-unaffected women ≥ 18 years and with no prior OC gene testing were ascertained through primary care in London. In-depth, semi-structured and 1:1 interviews were conducted until informational saturation was reached following nine interviews. Six interconnected themes emerged: health beliefs; decision making; factors influencing acceptability; effect on well-being; results communication; satisfaction. Satisfaction with testing was high and none expressed regret. All felt the telephone helpline was helpful and should remain optional. Delivery of low-risk results reduced anxiety. However, care must be taken to emphasise that low risk does not equal no risk. The main facilitators were ease of testing, learning about children’s risk and a desire to prevent disease. Barriers included change in family dynamics, insurance, stigmatisation and personality traits associated with stress/worry. PGT for personalised OC risk prediction in women in the general population had high acceptability/satisfaction and reduced anxiety in low-risk individuals. Facilitators/barriers observed were similar to those reported with genetic testing from high-risk cancer clinics and unselected PGT in the Jewish population.

The Polyscore of autonomic parameters predicts mortality and identifies low-risk individuals among diabetic survivors of acute myocardial infarction

Survivors of an acute myocardial infarction with diabetes mellitus retain an increased mortality risk. Reliable assessment of individual risk is required for effective and cost-efficient medical care in these patients. The Polyscore is a previously established risk predictor consisting of seven autonomic tests derived from electrocardiogram, blood pressure, and respiration. The Polyscore allows classification of survivors of myocardial infarction in groups at low, intermediate and high mortality risk. The aim of this study was to investigate the prognostic value of the Polyscore in diabetic survivors of acute myocardial infarction, which may be impaired by the presence of diabetic autonomic neuropathy. Survivors of an acute myocardial infarction were included in a prospective cohort study during hospitalisation due to the index event at two university hospitals in Munich, Germany. The Polyscore was determined from simultaneous non-invasive 30-min recordings of electrocardiogram, continuous arterial blood pressure, and respiration which were performed in all participants. Patients were followed for 5 years. The primary and secondary outcomes were all-cause mortality and cardiac mortality. 184 of 941 enrolled patients (19.6%) suffered from diabetes mellitus. 5-year-mortality was higher in diabetic patients (15.2%) compared to non-diabetic patients (5.8%). A multivariable Cox regression model confirmed the Polyscore as a strong predictor of mortality in diabetic post-MI patients (intermediate risk: HR 6.56, 95% CI 1.61–26.78, p = 0.004, mortality 22.8%; high risk: HR 18.76, 95% CI 4.35–80.98, p < 0.001, mortality 68.8%). There was no interaction between diabetes mellitus and the Polyscore regarding mortality prediction (p = 0.775). Interestingly, in contrast to the groups at intermediate and high risk (73 patients, 39.7%), the Polyscore identified a majority of diabetic patients (111, 60.3%) with a low mortality risk, comparable to that of low-risk non-diabetic patients (3.6% and 2.1%, respectively, p = 0.339). Consistent results were observed for cardiac mortality. This analysis shows that the Polyscore predicts all-cause and cardiac mortality in diabetic survivors of acute myocardial infarction. Within these patients it identifies a large population not affected by the excess mortality associated with diabetes in this setting. Thus, the Polyscore may facilitate risk-adapted follow-up strategies in diabetic survivors of myocardial infarction.

A new risk model based on a 11-m6A-related lncRNA signature for predicting prognosis and monitoring immunotherapy for gastric cancer

ObjectiveN6-methyladenosine (m6A) mRNA modification triggers malignant behaviors of tumor cells and thereby drives malignant progression in gastric cancer (GC). However, data regarding the prognostic values of m6A RNA methylation-related long non-coding RNAs (lncRNAs) in GC are very limited in the literature. We aimed to investigate the prognostic potential of m6A-related lncRNAs in predicting prognosis and monitoring immunotherapy efficacy in GC patients.MethodsTranscriptome and clinical data were obtained from GC biopsies from Cancer Genome Atlas (TCGA). M6A-related lncRNAs associated with GC were identified by constructing a co-expression network, and the gene pairs differentially expressed in GC were selected using univariate analysis. We constructed a risk model based on prognosis-related lncRNA pairs selected using the LASSO algorithm and quantified the best cutoff by comparing the area under the curve (AUC) for risk stratification. A risk model with the optimal discrimination between high- and low-risk GC patients was established. Its feasibility for overall survival prediction and discrimination of clinicopathological features, tumor-infiltrating immune cells, and biomarkers of immune checkpoint inhibitors between high- and low-risk groups were assessed.ResultsFinally, we identified 11 m6A-related lncRNA pairs associated with GC prognosis based on transcriptome analysis of 375 GC specimens and 32 normal tissues. A risk model was constructed with an AUC of 0.8790. We stratified GC patients into high- and low-risk groups at a cutoff of 1.442. As expected, patients in the low-risk group had longer overall survival versus the high-risk group. Infiltration of cancer-associated fibroblasts, endothelial cells, macrophages, particularly M2 macrophages, and monocytes was more severe in high-risk patients than low-risk individuals, who exhibited high CD4+ Th1 cell infiltration in GC. Altered expressions of immune-related genes were observed in both groups. PD-1 and LAG3 expressions were found higher in low-risk patients than high-risk patients. Immunotherapy, either single or combined use of PD-1 or CTLA4 inhibitors, had better efficacy in low-risk patients than high-risk patients.ConclusionThe new risk model based on a 11-m6A-related lncRNA signature can serve as an independent predictor for GC prognosis prediction and may aid in the development of personalized immunotherapy strategies for patients.

Appropriateness of Proton-Pump Inhibitor Usage among Hospitalized Patients in a Johor Government Hospital

Introduction: Proton pump inhibitors (PPIs) are potent and effective acid suppressant agents. There are emerging concerns that PPI overuse leads to escalating healthcare costs, drug-drug interactions, and adverse clinical outcomes. Exploring the appropriateness of PPI therapy among hospitalised patients in Malaysia is crucial. Thus, this study aims to determine the appropriateness of proton pump inhibitors utilisation in Sultan Ismail Hospital, Malaysia. Materials and Methods: This single-center retrospective cross-sectional study was conducted at a public tertiary hospital situated in the Johore state of Malaysia. Patients recruited were 12 years and above who had received PPI in January 2017. Medical information was reviewed from electronic medical records. Patients were classified into three subgroups based on indications adopted from evidence-based guidelines. Results: 422 patients were enrolled, 47.4% (n=200) fulfilled the Food Drug Administration (FDA) approved indications, 25.4% (n=107) had borderline indications, and 27.2% (n=115) had inappropriate PPI usage. Improper PPI therapy was observed with a similar fraction of patients in medical (24.5%, n= 58 ) and non-medical disciplines (30.8 %, n=57). Stress ulcer prevention in low-risk subjects and individuals with no apparent indication were reasons for PPI overuse. Conclusion: PPI overuse is prevailing in hospitalised adult patients. Promoting the awareness of guideline-based indications and adverse clinical events of PPI among clinicians is imperative in improving PPI prescribing.

Low-dose computed tomography lung cancer screening: Clinical evidence and implementation research.

Lung cancer causes more deaths than breast, cervical, and colorectal cancer combined. Nevertheless, population‐based lung cancer screening is still not considered standard practice in most countries worldwide. Early lung cancer detection leads to better survival outcomes: patients diagnosed with stage 1A lung cancer have a >75% 5‐year survival rate, compared to <5% at stage 4. Low‐dose computed tomography (LDCT) thorax imaging for the secondary prevention of lung cancer has been studied at length, and has been shown to significantly reduce lung cancer mortality in high‐risk populations. The US National Lung Screening Trial reported a 20% overall reduction in lung cancer mortality when comparing LDCT to chest X‐ray, and the Nederlands‐Leuvens Longkanker Screenings Onderzoek (NELSON) trial more recently reported a 24% reduction when comparing LDCT to no screening. Hence, the focus has now shifted to implementation research. Consequently, the 4‐IN‐THE‐LUNG‐RUN consortium based in five European countries, has set up a large‐scale multicenter implementation trial. Successful implementation of and accessibility to LDCT lung cancer screening are dependent on many factors, not limited to population selection, recruitment strategy, computed tomography screening frequency, lung‐nodule management, participant compliance, and cost effectiveness. This review provides an overview of current evidence for LDCT lung cancer screening, and draws attention to major factors that need to be addressed to successfully implement standardized, effective, and accessible screening throughout Europe. Evidence shows that through the appropriate use of risk‐prediction models and a more personalized approach to screening, efficacy could be improved. Furthermore, extending the screening interval for low‐risk individuals to reduce costs and associated harms is a possibility, and through the use of volumetric‐based measurement and follow‐up, false positive results can be greatly reduced. Finally, smoking cessation programs could be a valuable addition to screening programs and artificial intelligence could offer a solution to the added workload pressures radiologists are facing.

A Risk Model Based on Immune-Related Genes Predicts Prognosis and Characterizes the Immune Landscape in Esophageal Cancer.

Aberrant immune gene expression has been shown to have close correlations with the occurrence and progression of esophageal cancer (EC). We aimed to generate a prognostic signature based on immune-related genes (IRGs) capable of predicting prognosis, immune checkpoint gene (ICG) expressions, and half-inhibitory concentration (IC50) for chemotherapy agents for EC patients. Transcriptome, clinical, and mutation data on tumorous and paratumorous tissues from EC patients were collected from The Cancer Genome Atlas (TCGA) database. Then, we performed differential analysis to identify IRGs differentially expressed in EC. Their biofunctions and related pathways were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. These gene expression profiling data were merged with survival information and subjected to univariate Cox regression to select prognostic genes, which were then included in a Lasso-Cox model for signature generation (risk score calculation). Patients were divided into the high- and low-risk groups using the median risk score as a cutoff. The accuracy of the signature in overall survival prediction was assessed, so were its performances in predicting ICG expressions and IC50 for chemotherapy and targeted therapy agents and immune cell landscape characterization. Fifteen prognostic IRGs were identified, seven of which were optimal for risk score calculation. As expected, high-risk patients had worse overall survival than low-risk individuals. Significant differences were found in tumor staging, immune cell infiltration degree, frequency of tumor mutations, tumor mutation burden (TMB), and immune checkpoint gene expressions between high- vs. low-risk patients. Further, high-risk patients exhibited high predicted IC50 for paclitaxel, cisplatin, doxorubicin, and erlotinib compared to low-risk patients. The seven-IRG-based signature can independently and accurately predict overall survival and tumor progression, characterize the tumor immune microenvironment (TIME) and estimate ICG expressions and IC50 for antitumor therapies. It shows the potential of guiding personalized treatment for EC patients.

Predictive Validity of Adolescent Callous-Unemotional Traits and Conduct Problems with Respect to Adult Outcomes: High- and Low-Risk Samples.

Current understanding of the predictive validity of callous-unemotional (CU) traits is limited by (a) the focus on externalizing psychopathology and antisocial behaviors, (b) a lack of long-term prospective longitudinal data, (c) samples comprised of high-risk or low-risk individuals. We tested whether adolescent CU traits and conduct problems were associated with theoretically relevant adult outcomes 12-18 years later. Participants were drawn from two studies: higher-risk Fast Track (FT; n = 754) and lower-risk Child Development Project (CDP; n = 585). FT: conduct problems positively predicted externalizing and internalizing psychopathology and partner violence, and negatively predicted health, wellbeing, and education. Three conduct problems × CU traits interaction effects were also found. CDP: CU traits positively predicted depression and negatively predicted health and education; conduct problems positively predicted externalizing and internalizing psychopathology and substance use, and negatively predicted wellbeing. CU traits did not provide incremental predictive validity for multiple adult outcomes relative to conduct problems.