Self-controlled Design Research Articles

Adverse health outcomes in offspring of parents with alcohol-related liver disease: Nationwide Danish cohort study.

Parental drinking can cause harm to the offspring. A parent's diagnosis of alcohol-related liver disease (ALD) might be an opportunity to reach offspring with preventive interventions. We investigated offspring risk of adverse health outcomes throughout life, their association with their parent's educational level and diagnosis of ALD. We used nationwide health registries to identify offspring of parents diagnosed with ALD in Denmark 1996 to 2018 and age- and sex-matched comparators (20:1). We estimated the incidence rate ratios (IRRs) of hospital contacts with adverse health outcomes, overall and in socioeconomic strata. We used a self-controlled design to examine whether health outcomes were more likely to occur during the first year after the parent's ALD diagnosis. The 60,804 offspring of parents with ALD had a higher incidence rate of hospital contacts from age 15 to 60 years for psychiatric disease, poisoning, fracture or injury, alcohol-specific diagnoses, other substance abuse, and of death than comparators. Associations were stronger for offspring with low compared to high socioeconomic position: The IRR for admission due to poisoning was 2.2 versus 1.0 for offspring of an ALD parent with a primary level versus a highly educated ALD parent. Offspring had an increased risk for admission with psychiatric disease and poisoning in the year after their parent's ALD diagnosis. For example, among offspring whose first hospital contact with psychiatric disease was at age 13 to 25 years, the IRR in the first year after their parent's ALD diagnosis versus at another time was 1.29 (95% CI 1.13, 1.47). Main limitation was inability to include adverse health outcomes not involving hospital contact. Offspring of parents with ALD had a long-lasting higher rate of health outcomes associated with poor mental health and self-harm that increased shortly after their parent's diagnosis of ALD. Offspring of parents of low educational level were particularly vulnerable. This study highlights an opportunity to reach out to offspring in connection with their parent's hospitalization with ALD.

Foundational model aided automatic high-throughput drug screening using self-controlled cohort study.

Developing medicine from scratch to governmental authorization and detecting adverse drug reactions (ADR) have barely been economical, expeditious, and risk-averse investments. The availability of large-scale observational healthcare databases and the popularity of large language models offer an unparalleled opportunity to enable automatic high-throughput drug screening for both repurposing and pharmacovigilance. To demonstrate a general workflow for automatic high-throughput drug screening with the following advantages: (i) the association of various exposure on diseases can be estimated; (ii) both repurposing and pharmacovigilance are integrated; (iii) accurate exposure length for each prescription is parsed from clinical texts; (iv) intrinsic relationship between drugs and diseases are removed jointly by bioinformatic mapping and large language model - ChatGPT; (v) causal-wise interpretations for incidence rate contrasts are provided. Using a self-controlled cohort study design where subjects serve as their own control group, we tested the intention-to-treat association between medications on the incidence of diseases. Exposure length for each prescription is determined by parsing common dosages in English free text into a structured format. Exposure period starts from initial prescription to treatment discontinuation. A same exposure length preceding initial treatment is the control period. Clinical outcomes and categories are identified using existing phenotyping algorithms. Incident rate ratios (IRR) are tested using uniformly most powerful (UMP) unbiased tests. We assessed 3,444 medications on 276 diseases on 6,613,198 patients from the Clinical Practice Research Datalink (CPRD), an UK primary care electronic health records (EHR) spanning from 1987 to 2018. Due to the built-in selection bias of self-controlled cohort studies, ingredients-disease pairs confounded by deterministic medical relationships are removed by existing map from RxNorm and nonexistent maps by calling ChatGPT. A total of 16,901 drug-disease pairs reveals significant risk reduction, which can be considered as candidates for repurposing, while a total of 11,089 pairs showed significant risk increase, where drug safety might be of a concern instead. This work developed a data-driven, nonparametric, hypothesis generating, and automatic high-throughput workflow, which reveals the potential of natural language processing in pharmacoepidemiology. We demonstrate the paradigm to a large observational health dataset to help discover potential novel therapies and adverse drug effects. The framework of this study can be extended to other observational medical databases.

First-Generation Antihistamines and Seizures in Young Children

The widespread use of antihistamines in children for treatment of common cold symptoms and their central nervous system effects, like drowsiness, underscore the importance of being aware of the associated risks. To assess associations between prescriptions of first-generation antihistamines and seizures in children using a comprehensive and nationwide dataset. This cohort study used a self-controlled case-crossover design. Data were obtained from the National Health Insurance Service database in Korea. Children born between January 1, 2002, and December 31, 2005, who visited the emergency department for seizure events (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes R56.8, G40, and G41) during the follow-up period were included. Follow-up was completed on December 31, 2019, and data were analyzed from June 3, 2023, to January 30, 2024. First-generation antihistamine prescription. Primary outcome consisted of an index seizure event. Odds ratios (ORs) for seizure events were estimated using a conditional logistic regression model, comparing first-generation antihistamine prescription 1 to 15 days before seizure (hazard period) against control period 1 (31-45 days before the event) and control period 2 (61-75 days before the event) using the same period windows. Stratified analyses were conducted to examine the association with individual participant characteristics. Of 11 729 children who had a seizure event, 3178 (1776 [55.9%] boys) were identified as having been prescribed antihistamines during the hazard or the control period, but not both. Seizure events were predominantly observed in children aged 6 to 24 months (985 [31.0%]) and 25 months to 6 years (1445 [45.5%]). During the hazard period, 1476 first-generation antihistamine prescriptions were recorded, in contrast to 1239 and 1278 prescriptions during control periods 1 and 2, respectively. After multiple confounder adjustments, first-generation antihistamine prescription was associated with an increased seizure event risk during the hazard period (adjusted OR [AOR], 1.22 [95% CI, 1.13-1.31]). Stratified subgroup analyses showed consistent results, particularly in children aged 6 to 24 months who were prescribed first-generation antihistamines having a higher risk (AOR, 1.49 [95% CI, 1.31-1.70]) than children aged 25 months to 6 years (AOR, 1.11 [95% CI, 1.00-1.24]; P = .04 for interaction). Furthermore, sensitivity analyses, including adjustment for exposure window periods, evaluation of new first-generation antihistamine prescriptions, comparison of control points from the same period 1 year prior, and exclusion of individuals using combination drugs, confirmed a similarly high risk. In this cohort study, prescriptions for first-generation antihistamines were associated with a 22.0% higher seizure risk in children, especially in those aged 6 to 24 months. These findings emphasize the need for careful and judicious prescription of first-generation antihistamines in young children and underline the need for further research to elucidate associations between antihistamine prescriptions and seizure risk.

Enhancing lower limb and core muscle activation with blood flow restriction training: a randomized crossover study on high-intensity squat exercises.

The primary objective of this study was to assess the impact of high-intensity deep squat training integrated with various blood flow restriction (BFR) modalities on the activation of lower limb and core muscles. A randomized, self-controlled crossover experimental design was employed with 12 participants. The exercise protocol consisted of squat training at 75% of one-repetition maximum (1RM), performed in 3 sets of 8 repetitions with a 2-min inter-set rest period. This was conducted under four distinct BFR conditions: continuous low BFR (T1), intermittent medium BFR (T2), intermittent high BFR (T3), and a non-restricted control (C). Surface electromyography (EMG) was utilized to collect EMG signals from the target muscles during the BFR and squat training sessions. The root mean square (RMS) amplitude standard values were calculated for each squat set to quantify muscle activation levels, with these values expressed as a percentage of the maximum voluntary contraction (%MVC). Rating of Perceived Exertion was evaluated after each squat set, and leg circumference measurements were taken. 1) During the first two sets of deep squats, the %MVC of the vastus lateralis and vastus medialis in all compression groups was significantly higher than that in the control group (p < 0.05). Furthermore, in the first set, the %MVC of the vastus lateralis in Group T3 was significantly higher than in Group T2 (p < 0.05). In the third set, the %MVC of the vastus medialis in Groups T1 and T3 was significantly lower than in the first two sets (p < 0.05). 2) Group T1 showed an increased activation of the biceps femoris and semitendinosus muscles in the second and third sets, with %MVC values significantly greater than in the first set (p < 0.05). Group T2 only showed an increase in biceps femoris activation in the third set (p < 0.05). Group T3 significantly increased the activation of the biceps femoris and semitendinosus muscles only in the first set (p < 0.05). 3) No significant differences were observed in the changes of rectus abdominis %MVC among the groups (p > 0.05). In the first set, Group T3's erector spinae %MVC was significantly higher than the control group's; in the second set, it was significantly higher than both Group T2 and the control group's (p < 0.05). 4) After training, a significant increase in thigh circumference was observed in all groups compared to before training (p < 0.05). 5) For RPE values, Group T2's post-squat values were significantly higher than the control group's after all three sets (p < 0.05). Group T1's RPE values were also significantly higher than the control group's after the third set (p < 0.05). Groups T1, T2, and C all had significantly higher RPE values in the second and third sets compared to the first set (p < 0.05). All BFR modalities significantly enhanced the activation level of the anterior thigh muscles, with the continuous low BFR mode demonstrating a more stable effect. No significant differences were found in the activation level of the rectus abdominis among the groups. However, the intermittent high BFR mode was the most effective in increasing the activation level of the erector spinae muscles. While BFR did not further augment leg circumference changes, it did elevate subjective fatigue levels. The RPE was lowest during squatting under the intermittent high BFR condition.

Efficacy of oral testosterone undecanoate in children with androgen insensitivity syndrome

Objective: To investigate the efficacy and safety of oral testosterone therapy in individuals diagnosed with androgen insensitivity syndrome (AIS). Methods: A self-controlled study design was utilized, focusing on individuals with AIS who were genetically diagnosed at the Department of Endocrinology, Genetics, and Metabolism of Beijing Children's Hospital between 2009 and 2021. These patients underwent treatment involving the administration of testosterone. The primary observed indexes include the measurement of penis length, which should meet the minimal surgical standard (penis length≥2.5 cm) or greater than or equal to -2.5 s (lower limit of normal). Secondary observed indexes include penile length standard deviation score (PL-SDS), an increase in penis longitude (ΔPL), medication dosage, the course of therapy, and safety indicators, among others. There were 4 courses of treatment. After each course, patients were evaluated to determine whether termination of treatment was appropriate. Patients who exhibited inadequate post-treatment penile length growth were advised to continue with further treatment. The statistical methodology included t-test, and a Wilcoxon rank sum test to describe efficacy and safety. The patients were followed up until 2023. Results: The study comprised a total of 51 individuals with AIS, comprising 33 males and 18 females (gender of registered permanent residence). Among these patients, 10 were diagnosed with complete androgen insensitivity syndrome (CAIS) and 41 were diagnosed with partial androgen insensitive syndrome (PAIS). There were 2 children with CAIS were diagnosed by doctors and prescribed testosterone undecanoate, but the children did not really take medicine.The penile length of CAIS patients could not be measured (penile length<0.5 cm) before and after treatment. For PAIS patients, baseline penile length and PL-SDS were (2.3±0.6) cm and -3.7±1.3, respectively. The measurements for penile length and PL-SDS after each treatment course were recorded as follows: (2.7±0.8), (2.8±0.6), (2.6±0.4), (2.6±0.4) cm and -2.8±1.6, 2.5±1.6, 2.9±1.2, -3.2±0.9, respectively. Both penile length and PL-SDS interventions showed statistically significant gains when compared to the baseline performance of the 4 courses (t=4.05、3.56、2.55、2.23 and 3.88、3.50、2.50、2.19, all P<0.05). Before treatment, 13 PAIS patients (32%) reached 2.5 cm and seven (17%) reached greater than or equal to -2.5 s. Following the initial, subsequent, third, and fourth therapeutic interventions, 18 cases (44%), 24 cases (59%), 25 cases (61%), and 26 cases (63%) reached 2.5 cm, respectively. Additionally, A total of 12 cases (29%), 15 cases (37%), 20 cases (49%), and 21 cases (51%), respectively, were found to reach greater than or equal to -2.5 s. The study involved the longitudinal monitoring of patients with the highest recorded age being 13.7 years. The weight, height, body mass index, bone age/age, cholesterol, hemoglobin and so on were all within the normal range and the difference were not statistically significant (all P>0.05). All 49 patients were no abnormalities in blood electrolyte, liver and kidney function and thyroid function and no changes in precocious puberty, pubic hair growth, aggressive behavior, vulvar skin darkening, diarrhea or other conditions. Conclusions: Testosterone undecanote in children with CAIS was no effective. The initial course of treatment for patients with PAIS demonstrates observable enhancements in penile length and PL-SDS. For patients with inadequate penile length growth, continued treatment in subsequent courses (such as the second, third, and fourth courses) is recommended toenhance outcomes gradually. Testosterone undecanoate was safe and effective for the majority of individuals with PAIS patients, with few adverse effects and good treatment tolerance.

Multiomics of parkinsonism cynomolgus monkeys highlights significance of metabolites in interaction between host and microbiota

The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson’s disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis.

Overcoming Time-Varying Confounding in Self-Controlled Case Series with Active Comparators: Application and Recommendations.

Confounding by indication is a key challenge for pharmacoepidemiologists. Although self-controlled study designs address time-invariant confounding, indications sometimes vary over time. For example, infection might act as a time-varying confounder in a study of antibiotics and uveitis, because it is time-limited and a direct cause both of receiving antibiotics and uveitis. Methods for incorporating active comparators in self-controlled studies to address such time-varying confounding by indication have only recently been developed. In this paper we formalize these methods, and provide a detailed description for how the active comparator rate ratio can be derived in a self-controlled case series (SCCS): either by explicitly comparing the regression coefficients for a drug of interest and an active comparator under certain circumstances using a simple ratio approach, or through the use of a nested regression model. The approaches are compared in two case studies, one examining the association between thiazolidinediones and fractures, and one examining the association between fluoroquinolones and uveitis using the UK Clinical Practice Research DataLink. Finally, we provide recommendations for the use of these methods, which we hope will support the design, execution and interpretation of SCCS using active comparators and thereby increase the robustness of pharmacoepidemiological studies.

Applying two approaches to detect unmeasured confounding due to time-varying variables in a self-controlled risk interval design evaluating COVID-19 vaccine safety signals, using myocarditis as a case example.

We test the robustness of the self-controlled risk interval (SCRI) design in a setting where time between doses may introduce time-varying confounding, using both negative control outcomes (NCOs) and quantitative bias analysis (QBA). All vaccinated cases identified from 5 European databases between 1 September 2020 and end of data availability were included. Exposures were doses 1-3 of the Pfizer, Moderna, AstraZeneca, and Janssen COVID-19 vaccines; outcomes were myocarditis and otitis externa (NCO). The SCRI used a 60-day control window and dose-specific 28-day risk windows, stratified by vaccine brand and adjusted for calendar time. The QBA included two scenarios: (i) baseline probability of the confounder was higher in the control window and (ii) vice versa. The NCO was not associated with any of the COVID-19 vaccine types or doses except Moderna dose 1 (IRR = 1.09, 95%CI 1.01-1.09). The QBA suggested even the strongest literature-reported confounder (COVID-19; RRmyocarditis = 18.3) could only explain away part of the observed effect from IRR = 3 to IRR = 1.40. The SCRI seems robust to unmeasured confounding in the COVID-19 setting, although a strong unmeasured confounder could bias the observed effect upward. Replication of our findings for other safety signals would strengthen this conclusion.

Importance of Examining Incidentality in Vaccine Safety Assessment

The author believes that the principles of statistical methods for vaccine safety can be divided into three categories: comparison of adverse event incidence rates between vaccinated and unvaccinated groups, analysis of incidentality in the vaccinated group, and a combination of both. The first category includes the cohort study; the second, the self-controlled risk interval design (SCRI); and the third, the self-controlled case series method. A single p-value alone should not determine a scientific conclusion, and analysis should be performed using multiple statistical methods with different principles. The author believes that using both the cohort study and the SCRI for analysis is the best method to assess vaccine safety. When the cohort study may not detect a significant difference owing to a low incidence rate of an adverse event in the vaccinated group or a high one in the unvaccinated group, the SCRI may detect it. Because vaccines must have a higher level of safety than the pharmaceuticals used for treatment, vaccine safety is advisable to be assessed using methods that can detect a significant difference even for any value of the incidence rate of an adverse event. The author believes that the analyses of COVID-19 vaccine safety have areas for improvement because the proportion of papers that used the cohort study and the SCRI was negligible.

The Effect of COVID-19 Vaccination on Outpatient Antibiotic Prescribing in Older Adults: A Self-Controlled Risk-Interval Study.

Coronavirus disease 2019 (COVID-19) vaccination has been associated with reduced outpatient antibiotic prescribing among older adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the impact of COVID-19 vaccination on outpatient antibiotic prescribing in the broader population of older adults, regardless of SARS-CoV-2 infection status. We included adults aged ≥65 years who received their first, second, and/or third COVID-19 vaccine dose from December 2020 to December 2022. We used a self-controlled risk-interval design and included cases who received an antibiotic prescription 2-6 weeks before vaccination (pre-vaccination or control interval) or after vaccination (post-vaccination or risk interval). We used conditional logistic regression to estimate the odds of being prescribed (1) any antibiotic, (2) a typical "respiratory" infection antibiotic, or (3) a typical "urinary tract" infection antibiotic (negative control) in the post-vaccination interval versus the pre-vaccination interval. We accounted for temporal changes in antibiotic prescribing using background monthly antibiotic prescribing counts. 469 923 vaccine doses met inclusion criteria. The odds of receiving any antibiotic or a respiratory antibiotic prescription were lower in the post-vaccination versus pre-vaccination interval (aOR, .973; 95% CI, .968-.978; aOR, .961; 95% CI, .953-.968, respectively). There was no association between vaccination and urinary antibiotic prescriptions (aOR, .996; 95% CI, .987-1.006). Periods with high (>10%) versus low (<5%) SARS-CoV-2 test positivity demonstrated greater reductions in antibiotic prescribing (aOR, .875; 95% CI, .845-.905; aOR, .996; 95% CI, .989-1.003, respectively). COVID-19 vaccination was associated with reduced outpatient antibiotic prescribing in older adults, especially during periods of high SARS-CoV-2 circulation.

A comparison of four self-controlled study designs in an analysis of COVID-19 vaccines and myocarditis using five European databases

IntroductionThe aim of this study was to assess the possible extent of bias due to violation of a core assumption (event-dependent exposures) when using self-controlled designs to analyse the association between COVID-19 vaccines and myocarditis. MethodsWe used data from five European databases (Spain: BIFAP, FISABIO VID, and SIDIAP; Italy: ARS-Tuscany; England: CPRD Aurum) converted to the ConcePTION Common Data Model. Individuals who experienced both myocarditis and were vaccinated against COVID-19 between 1 September 2020 and the end of data availability in each country were included. We compared a self-controlled risk interval study (SCRI) using a pre-vaccination control window, an SCRI using a post-vaccination control window, a standard SCCS and an extension of the SCCS designed to handle violations of the assumption of event-dependent exposures. ResultsWe included 1,757 cases of myocarditis. For analyses of the first dose of the Pfizer vaccine, to which all databases contributed information, we found results consistent with a null effect in both of the SCRI and extended SCCS, but some indication of a harmful effect in a standard SCCS. For the second dose, we found evidence of a harmful association for all study designs, with relatively similar effect sizes (SCRI pre = 1.99, 1.40 – 2.82; SCRI post 2.13, 95 %CI – 1.43, 3.18; standard SCCS 1.79, 95 %CI 1.31 – 2.44, extended SCCS 1.52, 95 %CI = 1.08 – 2.15). Adjustment for calendar time did not change these conclusions. Findings using all designs were also consistent with a harmful effect following a second dose of the Moderna vaccine. ConclusionsIn the context of the known association between COVID-19 vaccines and myocarditis, we have demonstrated that two forms of SCRI and two forms of SCCS led to largely comparable results, possibly because of limited violation of the assumption of event-dependent exposures.

A Comparison of In Vitro Measurement and Ultrasound for Peripherally Inserted Central Catheter Placement in Premature Infants: A Before-and-After Self-Controlled Prospective Study.

Background This study aimed to investigate the effectiveness of ultrasonography (US) and in vitro measurement (IVM) methods in localizing peripherally inserted central catheters (PICCs) in premature infants and analyze the relevant factors affecting the accuracy of IVM. Methodology The study employs a prospective before-and-after self-controlled clinical trial design. A total of 210 premature infants who underwent PICC catheterization were compared. We assessed the rate of catheter tip placement, consistency, and stability and analyzed the relevant factors. Results The study enrolled a total of 202 premature infants after eight infants dropped out. The one-time positioning rates of the PICC catheter tip using US and IVM were 100% and 73.8%, respectively. Concerning IVM, 53 (26.2%) patients did not reach the optimal position, with 24 (11.8%) patients having a shallow position and 29 (14.3%) having a deep position. The consistency of the two methods was 0.782 (p < 0.05). The degree of dispersion of US was 0.2 (0.0-0.4) cm, which was significantly smaller than IVM at 1.5 (0.0-1.8) cm. Gestational age less than 32 weeks (odds ratio (OR) = 6.64, 95% confidence interval (CI) = 1.43-30.81), weight less than 1,500 g (OR = 5.85, 95% CI = 2.11-16.20), body length less than 40 cm (OR = 15.36, 95% CI = 4.47-52.72), mechanical ventilation (OR = 5.13, 95% CI = 1.77-14.83), abdominal distension (OR = 78.18, 95% CI = 10.62-575.22), and bloating (OR = 8.81, 95% CI = 1.42-47.00) were risk factors that affected the accuracy of IVM. Conclusions Gestational age, weight, length, mechanical ventilation, abdominal distension, and swelling can lead to deviations with IVM. US can directly view the tip of the catheter, which is more accurate. Additionally, it is recommended to reduce the length of the catheter by 1.3 cm when using IVM to achieve the best-estimated placement length.

Effect of virtual reality-based mindfulness training model on anxiety, depression, and cancer-related fatigue in ovarian cancer patients during chemotherapy.

Although the prognosis of ovarian cancer can be significantly improved through standardized surgery and chemotherapy, 70% of epithelial ovarian cancer (EOC) patients would suffer from drug resistance and recurrence during the long chemotherapy cycle. To explore the impact of a training mode based on the integration of virtual reality technology and mindfulness on anxiety, depression, and cancer-related fatigue in ovarian cancer patients during chemotherapy. Through virtual reality technology, a mindfulness training software was designed and developed, and a mindfulness training mode based on virtual reality technology was constructed. Using a self-controlled design, 48 ovarian cancer patients undergoing chemotherapy who were hospitalized in a tertiary hospital in Beijing from August 2022 to May 2023 were conveniently selected as the research subjects. The patients were subjected to four weeks of mindfulness training based on virtual reality technology, and the acceptance of the mindfulness training mode using virtual reality technology was evaluated. The Hospital Anxiety and Depression Scale (HADS) and Cancer Related Fatigue Scale (CRF) were used to evaluate the anxiety, depression, and fatigue of patients before and after intervention. The virtual reality based mindfulness training mode includes four functional modules: personalized curriculum, intelligent monitoring, emotion tracking, and Funny Games. 48 patients had a high acceptance score (139.21 ± 10.47), and after using mindfulness training mode based on virtual reality technology, anxiety, depression, and cancer-related fatigue in ovarian cancer patients during chemotherapy were significantly reduced, with a statistically significant difference (p< 0.001). Ovarian cancer patients during chemotherapy have a high acceptance of virtual reality based mindfulness training mode. The application of this mode can reduce the psychological problems of anxiety, depression, and cancer-related fatigue in ovarian cancer patients during chemotherapy, and is worth promoting and using.

Effectiveness of health education and counseling on stages of change, decisional balance, and smoking cessation self-efficacy: A prospective self-control study

ObjectiveTo examine the effectiveness of health education and counseling on the stages of change, decisional balance, and smoking cessations elf-efficacy in smokers with no intention of quitting. MethodsA prospective self-controlled design was conducted between December 2020 and December 2022. The research period was divided into a control stage (first to fourth weeks) and an experimental stage (fifth to eighth weeks). Patients with coronary artery disease (CAD) and habitually smoked were recruited. Pearson correlation and a one-factor repeated-measurement analysis were performed to assess the effectiveness of the intervention. ResultsIn total, 108 male CAD patients with a mean age of 58.1 years were recruited. After 4 weeks of the intervention, 55 (51%) exhibited behavior change (X 2 = 18.03, p = .001). The decisional balance and smoking cessation self-efficacy scores significantly improved in the experimental stage. No significant differences were observed in the control stage. ConclusionsFour weeks of health education and counseling could effectively improve participants’ stage of change, decisional balance, and smoking cessation self-efficacy. Practice implicationHealthcare professionals can play key roles in helping CAD patients successfully quit smoking through individual education and counseling.

Herb-drug interactions of silybinin and cilofexor in beagle dogs based on pharmacokinetics by UPLC-MS/MS.

Objective: A remarkably sensitive, accurate, and efficient ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was developed as a facile and expeditious method for measuring cilofexor concentration in beagle dogs, the herb-drug interactions between silybinin and cilofexor was explored based on pharmacokinetics. Methods: The plasma sample protein of the beagles were rapidly sedimented with acetonitrile, and cilofexor and tropifexor (internal standard, ISTD) were separated by gradient elution using a 0.1% formic acid aqueous solution and acetonitrile as the mobile phase. The concentrations were detected using positive ion multiple reaction monitoring (MRM) mode. Mass transfer pairs were m/z 587.91→267.91 for cilofexor and m/z 604.08→228.03 for ISTD, respectively. A two-period self-controlled experimental design was adopted for the HDIs experiment. In the first period (Group A), six beagle dogs were orally administered cilofexor at a dose of 1mg/kg. In the second period (Group B), silybinin (3mg/kg) was orally administered to the six beagle dogs twice a day for seven consecutive days, after which cilofexor was orally administered. The cilofexor concentration in beagle dogs was determined, and HDIs were evaluated based on their pharmacokinetics. Results: The accuracy and precision of cilofexor were both less than 15%, and the recoveries, matrix effects, and stability met the relevant requirements. The Cmax of cilofexor in group B was 49.62% higher than that in group A, whereas the AUC(0-t) and AUC(0-∞) of cilofexor in group B were 47.85% and 48.52% higher, respectively, than those in group A. Meanwhile, the t1/2 extended from 7.84h to 9.45 h, CL and Vz decreased in Group B. Conclusion: A novel UPLC-MS/MS approach was successfully applied for the measurement of cilofexor in beagle dog plasma. Silybinin can alter the pharmacokinetics of cilofexor in beagle dogs, thereby increasing plasma exposure to cilofexor.

Risk of Stroke and Myocardial Infarction Among Initiators of Triptans

Triptans are contraindicated in patients with ischemic heart disease or previous myocardial infarction, and caution is advised when prescribing these drugs to patients with vascular risk factors. However, controlled observational studies have either shown no association or an apparent lower risk, possibly owing to a channeling of triptans to individuals at low risk of cardiovascular outcomes, and it remains unclear whether avoiding triptan treatment for these patients is meaningful. To establish whether an association between triptans and ischemic events could be demonstrated using a self-controlled design because this type of design is robust to the previously mentioned type of confounding. All people in nationwide Danish registries who were initiating triptans and all the ischemic events that they experienced were identified. A case-crossover design was used to estimate odds ratios (OR) for associations between first-ever triptan use and ischemic outcomes, comparing triptan exposure in the 2-week period up to the event with four 2-week reference periods. Data were obtained for the period January 1995 to August 2022. Included from the population of Denmark were individuals redeeming a prescription for any triptan and experiencing at least 1 of 3 predefined ischemic outcomes. No one was excluded. Initiation of any triptan. Acute myocardial infarction, ischemic stroke, or nonspecified stroke. Identified were a total of 429 612 individuals (median [IQR] age, 38 [28-48] years; 325 687 female [75.8%]) who redeemed a first prescription for a triptan in the study period. Of these patients, 11 (0.003%) had a myocardial infarction with the first triptan prescription in either a focal or referent window (odds ratio [OR], 3.3; 95% CI, 1.0-10.9), 18 (0.004%) had ischemic stroke (OR, 3.2; 95% CI, 1.3-8.1), and 35 (0.008%) had ischemic/nonspecified stroke (OR, 3.0; 95% CI, 1.5-5.9). Case patients had a median age of approximately 60 years and had a high-risk cardiovascular profile. Results of this case-crossover study suggest that triptan initiation was associated with higher risk of ischemic stroke and myocardial infarction. For the individual patient with low background cardiovascular risk, the risk of an ischemic event after triptan initiation was very low.

Cardiovascular, Neurological, and Immunological Adverse Events and the 23-Valent Pneumococcal Polysaccharide Vaccine

Despite widespread immunization with the 23-valent pneumococcal polysaccharide vaccine (PPSV23), safety concerns remain owing to a lack of statistical power and largely outdated evidence. To evaluate the association between cardiovascular, neurological, and immunological adverse events and PPSV23 vaccination in older adults. This population-based cohort study using a self-controlled risk interval design used a large linked database created by linking the Korea Immunization Registry Information System and the National Health Information Database (2018 to 2021). Participants included patients aged 65 years or older with a history of PPSV23 vaccination and incident cardiovascular, neurological, or immunological events during the risk and control intervals. Data were analyzed from November 2022 to April 2023. 23-valent pneumococcal polysaccharide vaccine. The occurrence of 1 among 6 cardiovascular events (myocardial infarction, atrial fibrillation, cardiomyopathy, heart failure, hypotension, and myocarditis or pericarditis), 2 neurological events (Bell palsy and Guillain-Barré syndrome), and 3 immunological events (sepsis, thrombocytopenia, and anaphylaxis) during the risk and control periods. The risk and control intervals were defined as 1 to 28 and 57 to 112 days after PPSV23 vaccination, respectively. Conditional Poisson regression was used to estimate the incidence rate ratio (IRR) with a 95% CI. Altogether, 4355 of the 1 802 739 individuals who received PPSV23 vaccination and experienced at least 1 outcome event were included (mean [SD] age, 72.4 [8.2] years; 2272 male participants [52.1%]). For cardiovascular events, there were no significant associations for myocardial infarction (IRR, 0.96; 95% CI, 0.81-1.15), heart failure (IRR, 0.85; 95% CI, 0.70-1.04), and stroke (IRR, 0.92; 95% CI, 0.84-1.02). Similarly, no increased risks were observed for neurological and immunological outcomes: Bell palsy (IRR, 0.95; 95% CI, 0.72-1.26), Guillain-Barré syndrome (IRR, 0.27; 95% CI, 0.06-1.17), sepsis (IRR, 0.99; 95% CI, 0.74-1.32), and thrombocytopenia (IRR, 1.18; 95% CI, 0.60-2.35). In this self-controlled risk interval study, there was no appreciable increase in risk for most cardiovascular, neurological, or immunological adverse events following PPSV23. The updated safety profile of PPSV23 provides supportive evidence for the establishment of immunization strategies for older adults.

Effects of High-Load Bench Press Training with Different Blood Flow Restriction Pressurization Strategies on the Degree of Muscle Activation in the Upper Limbs of Bodybuilders.

Background: The aim of this study was to investigate the effects of different pressurization modes during high-load bench press training on muscle activation and subjective fatigue in bodybuilders. Methods: Ten bodybuilders participated in a randomized, self-controlled crossover experimental design, performing bench press training under three different pressurization modes: T1 (low pressure, high resistance), T2 (high pressure, high resistance), and C (non-pressurized conventional). Surface EMG signals were recorded from the pectoralis major, deltoid, and triceps muscles using a Delsys Trigno wireless surface EMG during bench presses. Subjective fatigue was assessed immediately after the training session. Results: (1) Pectoralis major muscle: The muscle activation degree of the T1 group was significantly higher than that of the blank control group during the bench press (p < 0.05). The muscle activation degree of the T2 group was significantly higher than that of the C group during the bench press (p < 0.05). In addition, the muscle activation degree of the T2 group was significantly higher than that of the T1 group during the first group bench press (p < 0.05). (2) Deltoid muscle: The muscle activation degree of the T2 group during the third group bench press was significantly lower than the index values of the first two groups (p < 0.05). The muscle activation degree in the experimental group was significantly higher than that in the C group (p < 0.05). The degree of muscle activation in the T2 group was significantly higher than that in the T1 group during the first bench press (p < 0.05). (3) Triceps: The muscle activation degree of the T1 group was significantly higher than the index value of the third group during the second group bench press (p < 0.05), while the muscle activation degree of the T2 group was significantly lower than the index value of the first two groups during the third group bench press (p < 0.05). The degree of muscle activation in all experimental groups was significantly higher than that in group C (p < 0.05). (5) RPE index values in all groups were significantly increased (p < 0.05). The RPE value of the T1 group was significantly higher than that of the C group after bench press (p < 0.05). The RPE value of the T1 group was significantly higher than that of the C group after bench press (p < 0.05). In the third group, the RPE value of the T1 group was significantly higher than that of the C and T2 groups (p = 0.002) (p < 0.05). Conclusions: The activation of the pectoralis major, triceps brachii, and deltoid muscles is significantly increased by high-intensity bench press training with either continuous or intermittent pressurization. However, continuous pressurization results in a higher level of perceived fatigue. The training mode involving high pressure and high resistance without pressurization during sets but with 180 mmHg occlusion pressure and pressurization during rest intervals yields the most pronounced overall effect on muscle activation.

Zinc supplementation with polaprezinc was associated with improvements in albumin, prothrombin time activity, and hemoglobin in chronic liver disease.

Zinc deficiency occurs in a variety of diseases, including chronic liver disease (CLD). We investigated the correlation between zinc levels and biochemical and hematological tests in CLD and the effect of zinc supplementation with polaprezinc on these values. The first study (Study 1) was a retrospective observational study of 490 patients with CLD not receiving zinc supplementation, with data available from September 2009 to August 2021. Univariate and multiple regression analysis showed that serum zinc levels correlated most strongly with albumin (Alb) and also significantly with prothrombin time activity (PT%) and hemoglobin (Hb). A subsequent study (Study 2) focused on patients with advanced CLD who used polaprezinc for more than 90 days between January 2005 and August 2021. Using a self-controlled design with the 6-month period prior to polaprezinc as the control period, comparisons showed that Alb (p<0.0001), PT% (p<0.0005), and Hb (p<0.01) were significantly improved in the polaprezinc-treated patients compared to the control group. In conclusion, serum zinc levels were correlated with serum Alb, Hb, and PT% in patients with CLD, and zinc supplementation with polaprezinc was associated with improvements in Alb, Hb, and PT% within at least 6 months.

The effectiveness of a workplace violence prevention strategy based on situational prevention theory for nurses in managing violent situations: a quasi-experimental study

BackgroundWorkplace violence (WPV) poses a significant occupational hazard for nurses. The efficacy of current education and training programs in mitigating WPV incidence among nurses remains uncertain, possibly due to insufficient consideration of clinical contexts and nurses’ specific needs. Therefore, this study developed a WPV prevention strategy based on the actual requirements of clinical nurses and situational prevention theory and aimed to explore its application effects.MethodsUnder the guidance of situational prevention theory, a WPV prevention strategy for nurses was constructed through literature review, semi-structured interviews and focus group discussion. This study adopted a self-controlled research design, and trained 130 nurses selected from a comprehensive tertiary grade A hospital in Suzhou in this WPV prevention strategy. Data were collected through structured questionnaires, including the revised WPV questionnaire, WPV severity grading scale, and hospital WPV coping resources scale. The WPV incidence, severity, and WPV coping resource scores of nurses were collected before the intervention, as well as at 3 months, 6 months, and 9 months after training.ResultsThe WPV prevention strategy comprised 11 prevention plans based on 11 high-risk situational elements of WPV. Each prevention plan included the WPV prevention flowchart, treatment principle, and communication strategy. The strategy demonstrated excellent feasibility and practicality. Following the intervention, the overall incidence of WPV among nurses significantly decreased from 63.85% (baseline) to 46.15% (9 months after training) (P < 0.05). After the training, the severity of psychological violence (Wald χ² = 20.066, P < 0.001) and physical violence (Wald χ² = 9.100, P = 0.028) reported by nurses decreased compared to the baseline (P < 0.05). Moreover, the overall WPV coping resource score significantly increased from [66.50 (57.00, 77.25) points] (baseline) to [80.00 (68.00, 97.25) points] (9 months after training) (P < 0.05).ConclusionsThe described WPV prevention strategy, grounded in situational prevention theory and tailored to the needs of clinical nurses, effectively reduced WPV incidence, mitigated its severity, and enhanced nurses’ WPV coping resources. This approach offered new avenues for nurses in the prevention of WPV.