Background
Despite Helicobacter pylori (HP) eradication, individuals can still develop gastric cancer (GC). Prior studies have demonstrated that nonaspirin nonsteroidal anti‐inflammatory drugs ...(NA‐NSAIDs) reduce the risk of GC, but this may be caused by immortal time bias and failure to adjust for HP status. The objective of this study was to investigate whether NA‐NSAIDs reduced the risk of GC in patients who undergo H. pylori eradication.
Methods
Adult patients who had received clarithromycin‐based triple therapy between 2003 and 2016 were identified from a territory‐wide health care database. Exclusion criteria included prior GC or GC diagnosed <6 months after HP eradication, prior gastrectomy, gastric ulcer after HP eradication, and failure of triple therapy. Covariates included age, sex, prior peptic ulcer disease, other comorbidities, and concurrent medications (aspirin, proton pump inhibitors, statins, and metformin). To avoid immortal time bias, NA‐NSAID use (≥90 days) was treated as a time‐dependent variable in a multivariable Cox model (time‐dependent analysis). Time‐independent analysis was also performed.
Results
During a median follow‐up of 8.9 years (interquartile range, 5.4‐12.6 years), 364 of 92,017 patients (0.4%) who underwent HP eradication developed GC. NA‐NSAID use was associated with a significant reduction in the risk of GC in time‐fixed analysis (adjusted hazard ratio aHR, 0.65; 95% CI, 0.47‐0.90), but not in time‐dependent multivariable analysis (aHR, 1.35; 95% CI, 0.97‐1.87). Time‐dependent subgroup analyses also did not indicate any significant association between NA‐NSAID use and either cardia GC (aHR, 0.75; 95% CI, 0.27‐2.06) or noncardia GC (aHR, 1.28; 95% CI, 0.83‐1.98).
Conclusions
NA‐NSAID use was not associated with a reduced risk of GC among patients who underwent HP eradication. The chemopreventive effect of NA‐NSAIDs observed in prior studies may have been confounded by immortal time bias.
After comprehensively addressing multiple biases, the current results do not support a chemopreventive role of nonaspirin nonsteroidal anti‐inflammatory drugs in gastric cancer development among Helicobacter pylori‐eradicated patients.
•Use of Oral anticoagulants (OACs) is associated with reduced risk of dementia.•Maximizing time in therapeutic range could improve cognitive function in warfarin users.•OACs are useful not only for ...stroke prevention, but also for protection against dementia.•Methodological issues and the small number of studies limit the evidence.
Atrial fibrillation (AF) is a documented risk factor for dementia. However, it is unclear whether oral anticoagulant (OAC) treatment can reduce the development of dementia or cognitive impairment. We conducted a systematic review and meta-analysis of the association between OAC use and subsequent dementia development in AF patients by searching databases from their inception to February 2018 without language restriction. Six studies (one randomized controlled trial and five observational studies) met the inclusion criteria. The pooled adjusted risk ratios (RRs) suggested a protective effect of OAC use in reducing dementia risk (RR 0.79 95% CI: 0.67 – 0.93, I2 = 59.7%; P = 0.005). Further, high percentage of time in therapeutic range (TTR) was associated with a decreased risk of dementia (RR 0.38 95% CI 0.22-0.64, I2 = 81.8%; P < 0.001). Our results support the hypothesis that AF-related dementia may be due to silent brain infarcts and micro-embolism that could be prevented by OAC use. Future studies with prospective follow-up with direct comparison of vitamin K antagonists and direct oral anticoagulants are needed.
Reducing the burden of late-life morbidity requires an understanding of the mechanisms of ageing-related diseases (ARDs), defined as diseases that accumulate with increasing age. This has been ...hampered by the lack of formal criteria to identify ARDs. Here, we present a framework to identify ARDs using two complementary methods consisting of unsupervised machine learning and actuarial techniques, which we applied to electronic health records (EHRs) from 3,009,048 individuals in England using primary care data from the Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics admitted patient care dataset between 1 April 2010 and 31 March 2015 (mean age 49.7 years (s.d. 18.6), 51% female, 70% white ethnicity). We grouped 278 high-burden diseases into nine main clusters according to their patterns of disease onset, using a hierarchical agglomerative clustering algorithm. Four of these clusters, encompassing 207 diseases spanning diverse organ systems and clinical specialties, had rates of disease onset that clearly increased with chronological age. However, the ages of onset for these four clusters were strikingly different, with median age of onset 82 years (IQR 82-83) for Cluster 1, 77 years (IQR 75-77) for Cluster 2, 69 years (IQR 66-71) for Cluster 3 and 57 years (IQR 54-59) for Cluster 4. Fitting to ageing-related actuarial models confirmed that the vast majority of these 207 diseases had a high probability of being ageing-related. Cardiovascular diseases and cancers were highly represented, while benign neoplastic, skin and psychiatric conditions were largely absent from the four ageing-related clusters. Our framework identifies and clusters ARDs and can form the basis for fundamental and translational research into ageing pathways.
•Deep learning provides efficient and accurate prediction of treatment response.•Transfer learning can be used in radiological task with insufficient image datasets.•Tumor microenvironment and ...signaling pathways are linked with radiological prediction.
Deep learning is promising to predict treatment response. We aimed to evaluate and validate the predictive performance of the CT-based model using deep learning features for predicting pathologic complete response to neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC).
Patients were retrospectively enrolled between April 2007 and December 2018 from two institutions. We extracted deep learning features of six pre-trained convolutional neural networks, respectively, from pretreatment CT images in the training cohort (n = 161). Support vector machine was adopted as the classifier. Validation was performed in an external testing cohort (n = 70). We assessed the performance using the area under the receiver operating characteristics curve (AUC) and selected an optimal model, which was compared with a radiomics model developed from the training cohort. A clinical model consisting of clinical factors only was also built for baseline comparison. We further conducted a radiogenomics analysis using gene expression profiles to reveal underlying biology associated with radiological prediction.
The optimal model with features extracted from ResNet50 achieved an AUC and accuracy of 0.805 (95% CI, 0.696–0.913) and 77.1% (65.6%-86.3%) in the testing cohort, compared with 0.725 (0.605–0.846)) and 67.1% (54.9%-77.9%) for the radiomics model. All the radiological models showed better predictive performance than the clinical model. Radiogenomics analysis suggested a potential association mainly with WNT signaling pathway and tumor microenvironment.
The novel and noninvasive deep learning approach could provide efficient and accurate prediction of treatment response to nCRT in ESCC, and benefit clinical decision making of therapeutic strategy.
The formulation of medicines for children remains a challenge. An ideal pediatric formulation must allow accurate dose administration and be in a dosage form that can be handled by the target age ...group. It is also important to consider the choices and the amount of excipients used in the formulation for this vulnerable age group. Although oral formulations are generally acceptable to most pediatric patients, they are not suitable for drugs with poor oral bioavailability or when a rapid clinical effect is required. In recent years, oral transmucosal delivery has emerged as an attractive route of administration for pediatric patients. With this route of administration, a drug is absorbed through the oral mucosa, therefore bypassing hepatic first pass metabolism and thus avoiding drug degradation or metabolism in the gastrointestinal tract. The high blood flow and relatively high permeability of the oral mucosa allow a quick onset of action to be achieved. It is a simple and non-invasive route of drug administration. However, there are several barriers that need to be overcome in the development of oral transmucosal products. This article aims to provide a comprehensive review of the current development of oral transmucosal delivery specifically for the pediatric population in order to achieve systemic drug delivery. The anatomical and physiological properties of the oral mucosa of infants and young children are carefully examined. The different dosage forms and formulation strategies that are suitable for young patients are discussed.
Display omitted
Diabetes mellitus is a systemic disease with complications that include sight-threatening diabetic retinopathy. It is essential to understand the risk factors of diabetic retinopathy before effective ...prevention can be implemented. The aim of this review was to examine the association between diabetic retinopathy and systemic risk factors.
A PubMed literature search was performed up to May 2016 to identify articles reporting associations between diabetic retinopathy and systemic risk factors; only publications written in English were included. Relevant articles were selected and analysed.
Patients with diabetic retinopathy were more likely to have poor glycaemic control as reflected by a higher glycated haemoglobin, longer duration of diabetes, and use of insulin therapy for treatment. For other systemic risk factors, hypertension was positively associated with prevalence and progression of diabetic retinopathy. No clear association between obesity, hyperlipidaemia, gender, or smoking with diabetic retinopathy has been established as studies reported inconsistent findings. Myopia was a protective factor for the development of diabetic retinopathy. Several genetic polymorphisms were also found to be associated with an increased risk of development of diabetic retinopathy.
Good glycaemic and blood pressure control remain the most important modifiable risk factors to reduce the risk of progression of diabetic retinopathy and vision loss.
Patients with diabetes are at a higher risk of pneumonia and pneumonia mortality. Sodium glucose co-transporter 2 inhibitors (SGLT2is), the latest class of glucose-lowering agents, were shown to ...reduce the risk of pneumonia in clinical trials. However, the real-world effectiveness of SGLT2is on the risk of pneumonia is largely unknown.
To investigate the associations between SGLT2is use and the risk of pneumonia and pneumonia mortality compared with dipeptidyl peptidase-4 inhibitors (DPP4is) using an electronic medical database in Hong Kong.
A retrospective cohort study. The "prevalent new-user" design was adopted to account for the previous exposure to the study drugs being compared. Propensity score (PS) matching (1:4) was used to balance the baseline characteristics of the 2 groups.
Electronic health data of type 2 diabetes patients using SGLT2is and DPP4is between 2015 and 2018 was collected from the Clinical Data Analysis and Reporting System.
Pneumonia incidence and mortality.
The PS-matched cohort consisted of 6664 users of SGLT2is and 26 656 users of DPP4is, with a mean follow-up of 3.8 years. Poisson regression showed that SGLT2is use was associated with lower risk of pneumonia compared with DPP4is with an absolute rate difference of 4.05 per 1000 person-years (95% CI, 2.61-5.51). The corresponding incidence rate ratio was 0.71 (95% CI, 0.62-0.81). Similar reduction in risk of pneumonia death was observed (hazard ratio 0.57; 95% CI, 0.42-0.77).
Compared with DPP4is, SGLT2is use was associated with a reduced risk of pneumonia and pneumonia mortality in a real-world setting.
Preventing hypoglycaemia is an essential component of diabetes self-management that is affected by patients' attitudes and perceptions. This study aimed to explore the hypoglycaemia problem-solving ...ability of patients who have diabetes mellitus and factors that determine their attitudes and perceptions towards their previous events.
A cross-sectional study was conducted between October 2017 and May 2018 in three Arab countries (Jordan, Saudi Arabia and Kuwait) in patients with diabetes mellitus, who were prescribed antidiabetic therapy and had experienced hypoglycaemic events in the past six months. The Hypoglycaemia Problem-Solving Scale was used in this study. This scale contains two subscales, problem orientation (six questions) and problem-solving skills (eighteen questions), using a five-point Likert scale (range 0-4). Multiple linear regression analysis was used to identify predictors of hypoglycaemia problem-solving abilities.
A total of 895 patients participated in this study from the three countries (300 in Jordan, 302 in Saudi Arabia, and 293 in Kuwait). The average age of the patients was 53.5 years (standard deviation = 13.7) and 52.4% (n = 469) were males. Patients had moderate overall problem-solving ability with a median score of 63.00 (interquartile range = 13.00). Patients' problem-solving skills score (68.1%) was better than their problem-orientation skills score (58.3%). The highest sub-scale scores were for detection control, setting problem-solving goals, and evaluating strategies, 75.0%. The lowest sub-scale score was for problem-solving perception and immediate management, 50.0%. Older age, being educated, being married, having T2DM, prescribed insulin therapy, and not having been admitted to hospital for hypoglycaemia were important predictors of patients' problem-solving ability (p < 0.05).
Healthcare professionals are advised to provide more education to patients on how to self-manage hypoglycaemic events. Specifically, they should focus on the overall problem-solving perception of hypoglycaemia and its immediate management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
