Improving the performance of deep learning models in predicting and classifying gamma passing rates with discriminative features and a class balancing technique: a retrospective cohort study.

BACKGROUND: The purpose of this study was to improve the deep learning (DL) model performance in predicting and classifying IMRT gamma passing rate (GPR) by using input features related to machine parameters and a class balancing technique. METHODS: A total of 2348 fields from 204 IMRT plans for patients with nasopharyngeal carcinoma were retrospectively collected to form a dataset. Input feature maps, including fluence, leaf gap, leaf speed of both banks, and corresponding errors, were constructed from the dynamic log files. The SHAP framework was employed to compute the impact of each feature on the model output for recursive feature elimination. A series of UNet++ based models were trained on the obtained eight feature sets with three fine-tuning methods including the standard mean squared error (MSE) loss, a re-sampling technique, and a proposed weighted MSE loss (WMSE). Differences in mean absolute error, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were compared between the different models. RESULTS: The models trained with feature sets including leaf speed and leaf gap features predicted GPR for failed fields more accurately than the other models (F(7, 147) = 5.378, p < 0.001). The WMSE loss had the highest accuracy in predicting GPR for failed fields among the three fine-tuning methods (F(2, 42) = 14.149, p < 0.001), while an opposite trend was observed in predicting GPR for passed fields (F(2, 730) = 9.907, p < 0.001). The WMSE_FS5 model achieved a superior AUC (0.92) and more balanced sensitivity (0.77) and specificity (0.89) compared to the other models. CONCLUSIONS: Machine parameters can provide discriminative input features for GPR prediction in DL. The novel weighted loss function demonstrates the ability to balance the prediction and classification accuracy between the passed and failed fields. The proposed approach is able to improve the DL model performance in predicting and classifying GPR, and can potentially be integrated into the plan optimization process to generate higher deliverability plans. TRIAL REGISTRATION: This clinical trial was registered in the Chinese Clinical Trial Registry on March 26th, 2020 (registration number: ChiCTR2000031276). https://clinicaltrials.gov/ct2/show/ChiCTR2000031276.

Cancer risk following onset of type 2 diabetes in New Zealanders with impaired glucose tolerance over 25 years: a matched prospective cohort study.

BACKGROUND: In people with prediabetes, the link between developing type 2 diabetes (T2D) and cancer risk among those with impaired glucose tolerance (IGT) remains uncertain. We examined this association in IGT individuals from primary care in South and West Auckland, New Zealand, spanning 1994-2019, assessing 5- and 10-year cancer risks. METHODS: Study cohorts were extracted from the Diabetes Care Support Service in Auckland, New Zealand, linking it with national registries for death, cancer, hospital admissions, pharmaceutical claims, and socioeconomic status. We compared cancer risks in individuals with IGT newly diagnosed with or without T2D within a 1-5-year exposure window. Employing tapered matching and landmark analysis to address potential confounding effects, we formed comparative IGT cohorts. Weighted Cox regression models were then employed to assess the association between T2D onset and 5- and 10-year cancer risks. RESULTS: The study included 26,794 patients with IGT, with 629 newly diagnosed with T2D within 5 years and 13,007 without such a diagnosis. Those progressing to T2D had similar 5-year cancer risk but significantly higher 10-year risk (HR 1.35; 95% CI 1.09-1.68). This association was stronger in older individuals, the socioeconomically deprived, current smokers, those with worse metabolic measures, and lower renal function. Patients with IGT of NZ European ethnicity had lower 10-year cancer risk. CONCLUSIONS: T2D diagnosis influences cancer risk in individuals with IGT. Developing risk scores for high-risk IGT individuals and implementing cancer screening and structured diabetes prevention, especially in deprived or minority ethnic populations, is essential.

Long-term impact of type 2 diabetes onset on dementia incidence rate among New Zealanders with impaired glucose tolerance: A tapered-matched landmark analysis over 25 years.

INTRODUCTION: We aimed to investigate the association between the onset of type 2 diabetes (T2D) and dementia incidence rates (IR) in the population with impaired glucose tolerance (IGT) identified in primary care in New Zealand (NZ) over 25 years. METHODS: Tapered matching and landmark analysis (accounting for immortal bias) were used to control for potential effects of known confounders. The association between T2D onset and 5- and 10-year IR of dementia was estimated by weighted Cox models. RESULTS: The onset of T2D was significantly associated with the 10-year IR of dementia, especially in the socioeconomically deprived, those of non-NZ European ethnicity, those currently smoking, and patients with higher metabolic measures. DISCUSSION: Our findings suggest that the onset of T2D is a significant risk factor for dementia in individuals with IGT. Dementia screening and structured diabetes prevention are vital in the population with IGT, particularly those from deprived or ethnic minority backgrounds. HIGHLIGHTS: Increased dementia incidence rate links with T2D onset in people with IGT. Significant incidence varied by ethnicity, socioeconomic status, and health factors. Results emphasize the diabetes manage and socioeconomic factors on dementia risk. Secondary analysis highlights the key role of vascular health in dementia prevention.

Could primary care records be used to identify women at risk of perinatal anxiety? A mixed-methods study.

BACKGROUND: Perinatal anxiety (PNA) occurs throughout the antenatal period or up to 1 year after childbirth, with a prevalence of 21%. AIM: To investigate if primary care records could be used to identify women at 'higher risk' of PNA. METHOD: Mixed-methods approach using quantitative and qualitative methods. Quantitative data analysis used Clinical Practice Research Datalink and IQVIA Medical Research Data to identify risk factors for PNA. Interviews explored the lived experiences of women with PNA about predisposing factors for PNA and acceptability of being informed of risk; and perspectives of primary healthcare professionals and Voluntary, Community, and Social Enterprise practitioners about risk communication. Interviews were conducted online, digitally recorded with consent, transcribed, and anonymised prior to analysis. Data were thematically analysed. Patient and clinical advisory groups informed each stage of the research. RESULTS: Women reflected on both positive and negative impacts of being identified at higher risk of PNA, a lack of understanding of how primary care records are used, and who has access to them. All interview participants suggested predisposing factors that would not be coded in primary care records. Quantitative analysis demonstrated that some predisposing factors for PNA can be identified in a woman's primary care records. Initial analysis suggests associations between PNA and infant health and healthcare use. CONCLUSION: While identification of higher risk of PNA may be acceptable, some factors that may contribute to PNA are not coded in primary care records. Identifying and managing PNA is needed to improve infant health.

Principle and experimental study of a combined teardrop and heart-shaped channel bluffbody valveless piezoelectric pump.

In this study, we have developed a piezoelectric pump with a combined teardrop- and heart-shaped channel based on the Coanda effect and bionics principle. The bluffbody consists of teardrop- and heart-shaped channels. The vibration and the pump flow rate are evaluated theoretically, and the flow conditions under different bluffbody heights and different main channel widths are simulated. The theoretical and simulation results show that the pump has uneven resistance to flow in forward and reverse directions, and the height of the teardrop bluffbody and the width main channel affect the flow in the channel. Test data show that under the same pressure, when the main channel is 5 mm and the bluffbody height is 8 mm, the pump flow rate is 460.8 ml/min. The pump alleviates the serious backflow problem through the fluid blocking structure and is expected to become an active driver of microfluidic devices.

Chronic pain-mental health comorbidity and excess prevalence of health risk behaviours: a cross-sectional study.

BACKGROUND: Chronic musculoskeletal pain and anxiety/depression are significant public health problems. We hypothesised that adults with both conditions constitute a group at especially high risk of future cardiovascular health outcomes. AIM: To determine whether having comorbid chronic musculoskeletal pain and anxiety/depression is associated with the excess prevalence of selected known cardiovascular health risk behaviours. METHOD: A cross-sectional survey of adults aged 35+ years randomly sampled from 26 GP practice registers in West Midlands, England. Respondents were classified into four groups based on self-reported presence/absence of chronic musculoskeletal pain (pain present on most days for six months) and anxiety or depression (Hospital Anxiety and Depression Score 11+). Standardised binomial models were used to estimate standardised prevalence ratios and prevalence differences between the four groups in self-reported obesity, tobacco smoking, physical inactivity, and unhealthy alcohol consumption after controlling for age, sex, ethnicity, deprivation, employment status and educational attainment. The excess prevalence of each risk factor in the group with chronic musculoskeletal pain-anxiety/depression comorbidity was estimated. FINDINGS: Totally, 14 519 respondents were included, of whom 1329 (9%) reported comorbid chronic musculoskeletal pain-anxiety/depression, 3612 (25%) chronic musculoskeletal pain only, 964 (7%) anxiety or depression only, and 8614 (59%) neither. Those with comorbid chronic musculoskeletal pain-anxiety/depression had the highest crude prevalence of obesity (41%), smoking (16%) and physical inactivity (83%) but the lowest for unhealthy alcohol consumption (18%). After controlling for covariates, the standardised prevalence ratios and differences for the comorbid group compared with those with neither chronic musculoskeletal pain nor anxiety/depression were as follows: current smoking [1.86 (95% CI 1.58, 2.18); 6.8%], obesity [1.93 (1.76, 2.10); 18.9%], physical inactivity [1.21 (1.17, 1.24); 14.3%] and unhealthy alcohol consumption [0.81 (0.71, 0.92); -5.0%]. The standardised prevalences of smoking and obesity in the comorbid group exceeded those expected from simple additive interaction.

Recent developments in wearable piezoelectric energy harvesters.

Wearable piezoelectric energy harvesters (WPEHs) have gained popularity and made significant development in recent decades. The harvester is logically built by the movement patterns of various portions of the human body to harvest the movement energy and immediately convert it into usable electrical energy. To directly power different microelectronic devices on the human body, a self-powered device that does not require an additional power supply is being created. This Review provides an in-depth review of WPEHs, explaining the fundamental concepts of piezoelectric technology and the materials employed in numerous widely used piezoelectric components. The harvesters are classed according to the movement characteristics of several portions of a person's body, such as pulses, joints, skin, and shoes (feet). Each technique is introduced, followed by extensive analysis. Some harvesters are compared, and the benefits and drawbacks of each technique are discussed. Finally, this Review presents future goals and objectives for WPEH improvement, and it will aid researchers in understanding WPEH to the point of more efficient wireless energy delivery to wearable electronic components.

Superior doxorubicin cellular delivery effect established by optically active mesoporous silica nanoparticles.

The impact of optically active biomaterials on drug delivery remains a vital and hot topic. To reveal special advantages of optically active mesoporous silica nanoparticles in delivering drug in cells, optically active mesoporous silica nanoparticles deliver doxorubicin (DOX) with chiral behavior in cancer cells was studied. The present work focused on two types of optically active mesoporous silica nanoparticles named as levorotatory optically active mesoporous silica nanoparticles (LOA-MSNs) and dextrorotatory optically active mesoporous silica nanoparticles (DOA-MSNs) and examined their effects on cellular DOX delivery in cancer cells. The obtained LOA-MSNs and DOA-MSNs were regular spheres with particle diameters ranging from 200 to 250 nm, and their shell layer was filled with interlaced channels. Our results indicated that LOA-MSNs and DOA-MSNs did not exhibit cytotoxicity towards MCF-7 cells and B16 cells. The cytotoxicity of DOX-loaded LOA-MSNs and DOX-loaded DOA-MSNs were stronger than DOX owing to the synergistic retention and accumulation effect of nanoparticles. More importantly, DOX-loaded DOA-MSNs presented stronger cytotoxicity due to the higher synergistic retention and accumulation effect of DOA-MSNs. These findings suggest that DOA-MSNs with superior cellular delivery of DOX have great potential to advance the development of optical anti-tumor delivery system.

All-cause, premature, and cardiovascular death attributable to socioeconomic and ethnic disparities among New Zealanders with type 1 diabetes 1994-2019: a multi-linked population-based cohort study.

BACKGROUND: New Zealand (NZ) research into type 1 diabetes mellitus (T1DM) mortality can inform policy and future research. In this study we aimed to quantify the magnitude to which ethnicity and socioeconomic disparities influenced mortality at the population level among people with Type 1 diabetes (T1DM) in Auckland, New Zealand (NZ). METHODS: The cohort data were derived from the primary care diabetes audit program the Diabetes Care Support Service (DCSS), and linked with national primary care, pharmaceutical claims, hospitalisation, and death registration databases. People with T1DM enrolled in DCSS between 1994-2018 were included. All-cause, premature, and cardiovascular mortalities were estimated by Poisson regression models with adjustment for population-level confounders. The mortality rates ratio (MRR) was standardized against the DCSS type 2 diabetes population. Mortality rates were compared by ethnic group (NZ European (NZE) and non-NZE) and socioeconomic deprivation quintile. The population attributable fraction (PAF) was estimated for ethnic and socioeconomic disparities by Cox regression adjusting for demographic, lifestyle, and clinical covariates. The adjusted slope index inequality (SII) and relative index of inequality (RII) were used to measure the socioeconomic disparity in mortalities. RESULTS: Overall, 2395 people with T1DM (median age 34.6 years; 45% female; 69% NZE) were enrolled, among whom the all-cause, premature and CVD mortalities were 6.69 (95% confidence interval: 5.93-7.53), 3.30 (2.77-3.90) and 1.77 (1.39-2.23) per 1,000 person-years over 25 years. The overall MRR was 0.39 (0.34-0.45), 0.65 (0.52-0.80), and 0.31 (0.24-0.41) for all-cause, premature and CVD mortality, respectively. PAF attributable to ethnicity disparity was not significantly different for mortality. The adjusted PAF indicated that 25.74 (0.84-44.39)% of all-cause mortality, 25.88 (0.69-44.69)% of premature mortality, 55.89 (1.20-80.31)% of CVD mortality could be attributed to socioeconomic inequality. The SII was 8.04 (6.30-9.78), 4.81 (3.60-6.02), 2.70 (1.82-3.59) per 1,000 person-years and RII was 2.20 (1.94-2.46), 2.46 (2.09-2.82), and 2.53 (2.03-3.03) for all-cause, premature and CVD mortality, respectively. CONCLUSIONS: Our results suggest that socioeconomic disparities were responsible for a substantial proportion of all-cause, premature and CVD mortality in people with T1DM in Auckland, NZ. Reducing socioeconomic barriers to management and self-management would likely improve clinical outcomes.

Antitumor Mechanism and Therapeutic Potential of Cordycepin Derivatives.

Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin N6 to improve the problem, cordycepin derivatives (3a-4c) were synthesized, and biological evaluation of compounds was studied. In this study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound 4a showed the most obvious inhibitory effect on MCF7 cells with an IC50 value of 27.57 ± 0.52 µM, which was much lower than cordycepin. Compound 4a showed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound 4a promoted apoptosis and blocked the cell cycle in the G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound 4a could down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3 and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound 4a induced the apoptosis of MCF7 cells through the mitochondrial pathway.

Out-of-set association analysis of lung cancer drugs and symptoms based on clinical case data mining.

BACKGROUND: There are 1.8 million lung cancer deaths worldwide, accounting for 18% of global cancer deaths, including 710,000 in China, accounting for 23.8% of all cancer deaths in China. OBJECTIVE: To explore the out-of-set association rules of lung cancer symptoms and drugs through text mining of traditional Chinese medicine (TCM) treatment of lung cancer, and form medical case analysis to analyze the experience of TCM syndrome differentiation in its treatment. METHODS: The medical records of all patients diagnosed with lung cancer in Nanjing Chest Hospital from January to December 2018 were collected, and the out-of-set association analysis was performed using the MedCase v5.2 TCM clinical scientific research auxiliary platform based on the frequent pattern growth enhanced association analysis algorithm. RESULTS: In terms of TCM treatment of lung cancer, the clinical symptoms with high correlation included cough, expectoration, chest distress, and white phlegm; and the drugs with high correlation included Pinellia ternata, licorice root, white Atractylodes rhizome, and Radix Ophiopogonis; with the prescriptions based on Erchen and Maimendong decoctions. CONCLUSION: This analytical study of the medical cases of TCM treatment for lung cancer was performed using data mining techniques, and the out-of-set association rules between clinical symptoms and drugs were analyzed, including the understanding of lung cancer in TCM. Moreover, the essence of experience in drug use was gathered, providing significant scientific guidance for the clinical treatment of lung cancer.

Applying sequence analysis to uncover 'real-world' clinical pathways from routinely collected data: a systematic review.

OBJECTIVES: This systematic review aims to elucidate the methodological practices and reporting standards associated with sequence analysis (SA) for the identification of clinical pathways in real-world scenarios, using routinely collected data. STUDY DESIGN AND SETTING: We conducted a methodological systematic review, searching five medical and health databases: MEDLINE, PsycINFO, CINAHL, EMBASE and Web of Science. The search encompassed articles from the inception of these databases up to February 28, 2023. The search strategy comprised two distinctive sets of search terms, specifically focused on sequence analysis and clinical pathways. RESULTS: 19 studies met the eligibility criteria for this systematic review. Nearly 60% of the included studies were published in or after 2021, with a significant proportion originating from Canada (n = 7) and France (n = 5). 90% of the studies adhered to the fundamental SA steps. The optimal matching (OM) method emerged as the most frequently employed dissimilarity measure (63%), while agglomerative hierarchical clustering using Ward's linkage was the preferred clustering algorithm (53%). However, it is imperative to underline that a majority of the studies inadequately reported key methodological decisions pertaining to SA. CONCLUSION: This review underscores the necessity for enhanced transparency in reporting both data management procedures and key methodological choices within SA processes. The development of reporting guidelines and a robust appraisal tool tailored to assess the quality of SA would be invaluable for researchers in this field.

Research on the performance of a valveless piezoelectric pump with a herringbone bluffbody.

Aiming to improve the output performance of a valveless piezoelectric pump, this article presents a valveless piezoelectric pump with a herringbone bluffbody. The bluffbody is herringbone shaped and distributed in a tapered chamber. The tapered chamber and the bluffbody create a large reverse resistance in the chamber, thus effectively mitigating the backflow problem of the valveless pump. The theoretical analysis determined the relationship between the flow rate and the flow resistance coefficient as well as the variation of the pump chamber volume. It was also concluded that the piezoelectric pump has the best output flow at intrinsic frequencies. Through simulation calculations, the effectiveness of the bluffbody structure in mitigating backflow in piezoelectric pumps is analyzed to provide a reference for experimental prototype design parameters. Finally, a range of prototypes is produced for experimentation. The experimental results show that the designed bluffbody shape can increase the return energy loss to effectively mitigate the return flow issues of the valveless piezoelectric pump, thus improving the output performance. The optimum output flow rate is 158.5 ml/min at 200 V and 52.5 Hz and the tapered chamber angle of 6°, and the bluffbody height, angle, and quantities are 2 mm, 40°, and 2, respectively. The construction of the valveless piezoelectric pump proposed in this research can be used as a reference for subsequent improvements in the performance of valveless piezoelectric pumps, and due to the high output performance, experimental studies can be carried out in applications such as dispensing and heat dissipation in electronic products.

Health Inequality in Eight Adverse Outcomes Over a 25-Year Period in a Multi-Ethnic Population in New Zealand Population with Impaired Glucose Tolerance and/or Impaired Fasting Glucose: An Age-Period-Cohort Analysis.

Purpose: We aimed to examine socioeconomic inequality (SI) in cause-specific outcomes among adults with impaired glucose tolerance (IGT) and/or Impaired fasting glucose (IFG) in New Zealand (NZ) over 25 years. Patients and Methods: A population-based open cohort was derived from Diabetes Care Support Service in NZ with national databases linkage. Patients aged ≥18 years with IGT and/or IFG were enrolled between 01/01/1994 and 31/07/2018 and followed up until death or 31/12/2018. Incident outcomes (all-cause, premature, cardiovascular, and cancer death; cardiovascular, myocardial infarction, stroke, heart failure, and end-stage kidney disease hospitalization) by demographic, anthropometric, socioeconomic status, clinical measurements, enrol-time-periods, and IGT/IFG were evaluated. Adjusted incidence rate ratios, absolute risk difference, and SI measurements (slope and relative index of inequality) were estimated using Age-Period-Cohort models. Results: 29,894 patients (58.5 (SD 14.3) years mean age; 52.2% female) were enrolled with 5.6 (IQR: 4.4-7.4) years of median follow-up. Mortality rates decreased, whereas hospitalization (except myocardial infarction) rates increased. SI was significant for each outcome. Higher mortality and hospitalization rates and worsened SI were common in men, older, the most deprived, and Maori patients, as well as patients with obesity, current smoking, with both IFG and IGT, and greater metabolic derangement (higher systolic blood pressure, lipids, and HbA1c, and lower level of mean arterial pressure). Conclusion: Enhanced management strategies are necessary for people with IGT and/or IFG to address persisting SI, especially for men, older people, current smokers, NZ European and Maori patients, patients with obesity, or with any abnormal metabolic measurements.

Research progress on the chemical components and pharmacological effects of Physalis alkekengi L. var. franchetii (Mast.) Makino.

Physalis Calyx seu Fructus is the dry calyx or the calyx with fruit of the Solanaceae plant Physalis alkekengi L. var. franchetii (Mast.) Makino, with a long history of use in medicine and food. However, despite its many potential therapeutic and culinary applications, P. alkekengi is not being exploited for these applications on a large scale. This study analysed various research related to the different chemical components of P. alkekengi, including steroids, flavonoids, alkaloids, phenylpropanoids, sucrose esters, piperazines, volatile oils, polysaccharides, amino acids, and trace elements. In addition, research related to the pharmacological activities of P. alkekengi, including its anti-inflammatory, anti microbial, antioxidative, hypoglycaemic, analgesic, anti-tumour, and immunomodulatory effects were investigated. Research articles from 1974 to 2023 were obtained from websites such as Google Scholar, Baidu Scholar, and China National Knowledge Infrastructure, and journal databases such as Scopus and PubMed, with the keywords such as Physalis alkekengi, components, effects, and activities. This study aims to provide a comprehensive understanding of the progress of phytochemical and pharmacological research on the phytochemical and pharmacological aspects of P. alkekengi and a reference for the better exploitation of P. alkekengi in the food and pharmaceutical industries.

Comparative observations on the squamous-columnar junction of Von Ebner's glandular duct at the bottom of vallate papillae in dogs, rats, mice and human.

BACKGROUND: This paper aims to comparatively observe similarities of squamous-columnar junction (SCJ) at the opening of Von Ebner's glandular ducts at the vallate papillae in dogs, mice, rats and humans, lay a foundation for the selection of the model in future study of the carcinogenesis in SCJ at vallate papillae. MATERIALS AND METHODS: The localization of the vallate papillae in three laboratory animals and humans was comparatively observed. The differences of SCJ at vallate papillae were comparatively observed by Alcian blue, immunohistochemistry and HE staining. RESULTS: Anatomically, the canine vallate papillae were most similar to those of humans in location, whereas mice and rats only had a single, Ω-shaped, vallate papilla lying directly anterior to the posterior border of the intermolar eminence. In histology, the SCJ of dogs lacked a transition zone similar to that of the human SCJ, and there was glandular epithelium secreting acidic mucus at the opening of the rats' Von Ebner's glandular ducts. All of this suggested that the histological structure of SCJ in rats and dogs is more distinct from that of humans, whereas the histological structure of SCJ at vallate papilla in mice was more similar. CONCLUSIONS: The structure of SCJ at vallate papilla in mice is most similar to that of humans, so we conclude that mouse is the most suitable model for studying tumorigenesis in SCJ at vallate papillae in these three common laboratory animals.

Real-world evidence that among atrial fibrillation patients warfarin is associated with reduced nonelective admissions compared with those on DOACs.

BACKGROUND: Randomized trials show inconsistent estimates on risks of direct-acting oral anticoagulants (DOACs) versus warfarin in bleeding and mortality for atrial fibrillation (AF) patients. Trials are confounded by additional DOAC adherence support, while warfarin has a low time in therapeutic range. Few real-world studies compared emergency hospitalization risk between DOAC and warfarin users in AF. This study aimed to determine emergency hospitalization risk for AF patients on DOACs or warfarin in real-world settings. METHODS: A tapered-matched real-world cohort extracted data from 412 English general practices' primary care records linked with emergency department (ED) and hospitalization data from the ECLIPSE database. AF patients with new DOAC or warfarin prescriptions were included. The primary outcome was all-cause ED attendance; the secondary outcomes were ED re-attendance, nonelective hospitalization, and rehospitalization within 12 months. Weighted Cox regression estimated relative risk difference. RESULTS: 39 201 DOAC patients were matched with 13 145 warfarin patients. DOAC patients had a 25% higher likelihood of attending ED (odds ratio 1.25; 95% confidence interval [CI] 1.01-1.55). DOAC use also associated with higher ED re-attendance, nonelective hospitalization, and rehospitalization within 12 months: 1.41 (95% CI 1.00-1.98), 1.26 (1.00-1.57), and 1.54 (1.01-2.34), respectively, with p-values < .05. CONCLUSIONS: DOACs for AF thromboprophylaxis are associated with the increased risk of ED attendance, recurrent hospitalization, and numerical rise in ED re-attendance and first nonelective hospitalization compared to warfarin. However, these real-world data cannot establish if this difference results from medication adherence, lack of regular DOAC clinic monitoring, unmeasured confounders, or fundamental agent efficacy disparities.

Use of non-surgical treatments on the journey to knee replacement in patients with knee osteoarthritis: a 10-year population-based case-control study.

AIM: To investigate temporal trends in primary care visits, physiotherapy visits, dispensed non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in knee osteoarthritis (OA) patients who have and have not undergone knee replacement. METHODS: We analysed 5665 OA patients from the Skåne Healthcare Register, Sweden, who underwent knee replacement between 2015 and 2019. Controls were OA patients without knee replacement, matched 1:1 by sex, age, time and healthcare level of initial OA diagnosis, and assigned a pseudo-index date corresponding to their case's knee replacement date. Annual prevalence and prevalence ratio of primary care and physiotherapy visits, dispensed NSAIDs and opioids (all for any cause) in the 10 years before knee replacement were estimated using Poisson regression. RESULTS: The annual prevalence of all-cause primary care visits, physiotherapy visits and opioid use was similar between cases and controls until 3 years before the index date when it started to increase among the cases. The year before the index date, the prevalence ratio (cases vs controls) for physiotherapy use was 1.8 (95% CI 1.7, 1.8), while for opioid use 1.6 (1.5, 1.7). NSAID use was consistently higher among cases, even 10 years before the index date when the prevalence ratio versus controls was 1.3 (1.2, 1.3), increasing to 1.8 (1.7, 1.9) in the year preceding the index date. CONCLUSIONS: Management of OA patients who have and have not undergone knee replacement appears largely similar except for higher use of NSAIDs in knee replacement cases. Symptomatic treatments start to increase a few years before the surgery in knee replacement cases.

Association Between Onset of Type 2 Diabetes and Risk of Atrial Fibrillation in New Zealanders With Impaired Glucose Tolerance Over 25 Years.

Background The association between the onset of type 2 diabetes (T2D) and atrial fibrillation (AF) risk in individuals with impaired glucose tolerance (IGT) remains unclear. This study aimed to investigate the relationship between the incident onset of T2D and 5- and 10-year (after the landmark period) risks of AF in people with IGT identified in South and West Auckland primary care settings between 1994 and 2019. Methods and Results We compared AF risk in patients with IGT with and without newly diagnosed T2D within a 1- to 5-year exposure window. Tapered matching and landmark analysis (to address immortal bias) were used to control for confounding variables. The cohorts incorporated 785 patients who had T2D newly diagnosed within 5 years from enrollment (landmark date) and 15 079 patients without a T2D diagnosis. Patients progressing to T2D exhibited significantly higher 5-year (after the landmark period) AF risk (hazard ratio [HR], 1.34 [95% CI, 1.10-1.63]) and 10-year (after the landmark period) AF risk (HR, 1.28 [95% CI, 1.02-1.62]) compared with those without incident T2D. The association was more pronounced among men, older patients, socioeconomically deprived individuals, current smokers, those with higher metabolic measures, and lower renal function. New Zealand European ethnicity was associated with a lower 5- and 10-year risk of AF. Conclusions This study found a mediating effect of T2D on the risk of AF in a population with IGT in New Zealand. The development of risk scores and future replication studies can help identify and guide management of individuals with IGT at the highest risk of AF following incident T2D.

Recent Advances in Anti-Atherosclerosis and Potential Therapeutic Targets for Nanomaterial-Derived Drug Formulations.

Atherosclerosis, the leading cause of death worldwide, is responsible for ≈17.6 million deaths globally each year. Most therapeutic drugs for atherosclerosis have low delivery efficiencies and significant side effects, and this has hampered the development of effective treatment strategies. Diversified nanomaterials can improve drug properties and are considered to be key for the development of improved treatment strategies for atherosclerosis. The pathological mechanisms underlying atherosclerosis is summarized, rationally designed nanoparticle-mediated therapeutic strategies, and potential future therapeutic targets for nanodelivery. The content of this study reveals the potential and challenges of nanoparticle use for the treatment of atherosclerosis and highlights new effective design ideas.