Eligible Patients Research Articles

Evaluating prescription of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in patients with diabetes and albuminuria.

Although guidelines recommend the use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) in patients with diabetes, hypertension, and albuminuria, their use remains suboptimal in several developed countries. Limited data are available on ACEi/ARB use in developing countries. Here, we assessed the use of ACEi/ARB and identified factors contributing to their underutilization at Hatyai Hospital, Thailand. This retrospective cross-sectional study was conducted using data from the Hatyai Hospital database. Adult patients with diabetes, hypertension, and albuminuria were included. Clinical data and laboratory results were extracted. Furthermore, this study recorded pre-specified conditions that influenced physicians' decisions regarding the prescription of ACEi/ARBs in patients who did not adhere to guidelines. Of 4,655 eligible patients, 500 patients were selected. The average age of the patients was 66.3 years, and 59.6% were female. The adherence rate was 72.4%. Multivariate logistic regression analysis found a significant association between non-adherence and chronic kidney disease (CKD) stage (OR = 1.29, 95% CI: 1.04-1.60, p = 0.019). The most common pre-specified condition contributing to non-adherence was "no condition identified" (69.8%). Among the cases of non-adherence, 21.7% were due to ACEi/ARB discontinuation after acute kidney injury, followed by hyperkalemia (5.1%) and a moderate increase in serum creatinine (4.3%). ACEi/ARB therapy was suboptimal in patients with diabetes, hypertension, and albuminuria. Non-adherence was associated with CKD stage, possibly because of concerns about adverse events and healthcare-related factors.

Zuberitamab, an innovative anti-CD20 monoclonal antibody, for patients with primary immune thrombocytopenia in China: a randomized, double-blind, placebo-controlled, phase 2 study

Primary immune thrombocytopenia (ITP) is an autoimmune disease, and rituximab (RTX) induces long-term effect as second-line treatments. Zuberitamab is an innovative anti-CD20 monoclonal antibody, which was first developed in China and launched in diffuse large B lymphoma. This study aimed to investigate the safety, efficacy, and anticipated therapeutic dose of zuberitamab in Chinese ITP patients. This randomised, double-blind, placebo-controlled, phase 2 study was conducted at 26 hospitals in China. Eligible patients were aged 18-70 years, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous treatment and had a pre-treatment platelet count of <30×109/L. Patients randomly received zuberitamab in a dose escalation (100/300/600mg) or placebo once-weekly for 4 weeks and followed up to 24 weeks. The primary endpoint is the proportion of patients with a platelet count ≥50×109/L at week 8. Secondary endpoints include the proportion of patients with platelet counts ≥50×109/L or ≥100×109/L at least once within week 12/24, the proportion of patients experiencing platelets increased twice more than baseline as well as ≥30×109/L at least once during the treatment. Adverse events, pharmacokinetic, B cell depletion and immunogenicity were also assessed. This study is registered with https://www.chictr.org.cn/as ChiCTR2100050513. From October 2021 to March 2023, 50 patients were screened for eligibility, of whom 32 patients were enrolled and randomly assigned to placebo (n=4), zuberitamab 100mg (n=10), 300mg (n=8) and 600mg (n=10) groups. The primary endpoint (PLT ≥50×109/L at week 8) was achieved by 40% of patients in the 100mg group, while none in the other groups. Within 12 weeks, the proportions of patients in each treatment group achieving at least one instance of platelet count ≥50×109/L or ≥100×109/L or an increase twice more than baseline as well as ≥30×109/L were (70%, 38%, 50%), (60%, 13%, 30%), and (80%, 50%, 70%) in zuberitamab 100/300/600mg groups, respectively. By week 24, the proportions of patients achieving these secondary endpoints remained relatively stable or showed a mild increase of around 10%. The anticipated therapeutic dose of zuberitamab was 100mg. The plasma concentration of zuberitamab showed an increasing trend with dose (100mg-600mg) and linear pharmacokinetic behavior. CD19+ B cells and CD20+ B lymphocytes rapidly declined to 0% within one week and consistently maintained reduced levels throughout the entire treatment phase in three groups. Adverse events occurred in all patients with most of them were mild to moderate, no severe infections occurred. A slight decrease in immunoglobulins was observed in the 600mg group, but gradually recovered at week 20. Three patients (2 in 100mg and 1 in 600mg group) were tested positive for anti-zuberitamab antibodies. We also observed that women, disease duration <12 months, and MAIPA+patients may have higher response rates. This study preliminarily confirmed that 100mg zuberitamab was safe and effective in treating ITP and was recommended to support further investigation. National Natural Science Foundation of China and Zhejiang Bioray Biopharmaceutical Co. Ltd.

Comparison of the Effectiveness and Safety of Clozapine Between Once-Daily and Divided Dosing Regimen in Patients With Treatment-Resistant Schizophrenia.

Clozapine is the most effective antipsychotic with respect to the incidence of discontinuation and is indicated for treatment-resistant schizophrenia. Although the recommendation for clozapine administration is divided dosing, once-daily dosing of clozapine is commonly prescribed in many countries. However, there is currently no clinical data comparing all-cause discontinuation between the 2 methods of administration of clozapine. To compare the all-cause discontinuation and safety of clozapine administration between once-daily and divided dosing regimens. This was a retrospective cohort study. Participants were patients with treatment-resistant schizophrenia who had received 300 to 600 mg/day of clozapine for at least 3 months. Data were collected from outpatient medical records at Somdet Chaopraya Institute of Psychiatry. Eligible patients were classified into 2 groups: once-daily dosing and divided dosing. The primary outcome was the all-cause discontinuation rate between groups. The duration of the study was 2 years. One hundred eighteen patients were included and analyzed in this study (once-daily dosing group: n = 58; divided dosing group: n = 60). There was no significant difference in all-cause discontinuation between the 2 groups (odds ratio 1.03; 95% confidence interval: [0.28, 3.79]: P = 1.00), or adverse events between groups. In patients with treatment-resistant schizophrenia, there were no significant differences in effectiveness or safety between once-daily and divided dosing of clozapine. Further prospective studies with larger sample sizes are required to confirm these findings.

Appropriateness of recommended chest compression depths for cardiopulmonary resuscitation based on chest computed tomography parameters among Thai population: A multicenter retrospective study

AimWe evaluated the appropriateness of various chest compression (CC) depths among Thai population by comparing the calculated heart compression fraction (HCF) using mathematical methods based on chest computed tomography (CT) measurements. MethodsThis multicenter retrospective cross-sectional study was conducted from September 2014 to December 2020. Chest parameters included external anteroposterior diameter (EAPD), internal anteroposterior diameter (IAPD), heart anteroposterior diameter (HAPD), and non-cardiac soft tissue measured at the level of maximum left ventricular diameter (LVmax). We compared the HCFs as calculated from CT parameters using different CC depths at 5 cm, 6 cm, 1/4 of EAPD, and 1/3 of EAPD, with further subgroup analysis stratified by sex and BMI. ResultsA total of 2927 eligible adult patients with contrast-enhanced chest CT were included. The study group had mean age of 60.1 ± 14.7 years, mean BMI of 22 ± 4.4 kg/m2, and were 57% males. The mean HCFs were 41.5%, 53.5%, 42.4%, and 62.6%, for CC depths of 50 mm, 60 mm, 1/4 of EAPD, and 1/3 of EAPD respectively. HCF was significantly lower in male patients for all CC depths. Advanced age and higher BMI showed significant correlation with lower HCF for CC depths of 50 mm and 60 mm. ConclusionThe CC depth measure of 50–60 mm demonstrated efficacy in maintaining HCF and coronary perfusion in the general population except for geriatric and obese individuals. Adjusting CC depth to 1/4–1/3 of the EAPD yielded better outcomes. Future research should prioritize determining individualized CC depths based on EAPD proportion.

Sex-Age Interplay Among Young Aged Egyptians With First Acute Myocardial Infarction.

The burden of modifiable risk factors in young Egyptian adults presenting with first acute myocardial infarction (AMI), sex differences, sex-age interplay, and its relationship with demographic, angiographic characteristics, and type of AMI is a good topic for discussion. The study enrolled 165 young (≤45 years old) consecutive, eligible patients diagnosed with first AMI (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction), for their demographic, angiographic, echocardiographic, and laboratory investigations and gender differences. Our population were 29-45 years old and 12.1% were females, most of whom had ST-elevation myocardial infarction; obesity in females and smoking in males were the most prevalent; and the younger the age of females presenting with AMI the more aggressive underlying risk factors and the more reduction in left ventricular ejection fraction. Most of the female culprit lesions were thrombotic and the severity of atherosclerotic culprit lesions correlated positively with blood pressure. The age paradox in young females (regarding left ventricular ejection fraction and the traditional risk factors) and the thrombotic nature of the culprit lesion mandate early intensive 1-year and 2-year preventive strategies against coronary heart disease (CHD) with special concern for obesity as the main trigger early in life with proper control of blood pressure. In males, smoking cessation programs are the main target to ameliorate the progress of CHD hand in hand with the other 1-year and 2-year preventive strategies of CHD.

Comparison of safety and efficacy between Nirmatrelvir-ritonavir and molnupiravir in the treatment of COVID-19 infection in patients with advanced kidney disease: a retrospective observational study

Nirmatrelvir-ritonavir is used in patients with coronavirus disease 2019 (COVID-19) with normal or mild renal impairment (eGFR ≥30ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease (eGFR <30ml/min per 1.73m2). We performed a retrospective territory-wide observational study evaluating the safety and efficacy of nirmatrelvir-ritonavir when compared with molnupiravir in the treatment of patients with COVID-19 with advanced kidney disease. We adopted target trial emulation using data from a territory-wide electronic health record database on eligible patients aged ≥18 years with advanced kidney disease (history of eGFR <30ml/min per 1.73m2) who were infected with COVID-19 and were prescribed with either molnupiravir or nirmatrelvir-ritonavir within five days of infection during the period from 16 March 2022 to 31 December 2022. A sequence trial approach and 1:4 propensity score matching was applied based on the baseline covariates including age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index (CCI), hospitalisation, eGFR, renal replacement therapy, comorbidities (cancer, respiratory disease, myocardial infarction, ischaemic stroke, diabetes, hypertension), and drug use (renin-angiotensin-system agents, beta blockers, calcium channel blockers, diuretics, nitrates, lipid lowering agents, insulins, oral antidiabetic drugs, antiplatelets, immuno-suppressants, corticosteroids, proton pump inhibitors, histamine H2 receptor antagonists, monoclonal antibody infusion) within past 90 days. Individuals were followed up from the index date until the earliest outcome occurrence, death, 90 days from index date or the end of data availability. Stratified Cox proportional hazards regression adjusted with baseline covariates was used to compare the risk of outcomes between nirmatrelvir-ritonavir recipients and molnupiravir recipients which include (i) all-cause mortality, (ii) intensive care unit (ICU) admission, (iii) ventilatory support, (iv) hospitalisation, (v) hepatic impairment, (vi) ischaemic stroke, and (vii) myocardial infarction. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (≤5; >5), and number of COVID-19 vaccine doses received (0-1; ≥2 doses). A total of 4886 patients were included (nirmatrelvir-ritonavir: 1462; molnupiravir: 3424). There were 347 events of all-cause mortality (nirmatrelvir-ritonavir: 74, 5.06%; molnupiravir: 273, 7.97%), 10 events of ICU admission (nirmatrelvir-ritonavir: 4, 0.27%; molnupiravir: 6, 0.18%), 48 events of ventilatory support (nirmatrelvir-ritonavir: 13, 0.89%; molnupiravir: 35, 1.02%), 836 events of hospitalisation (nirmatrelvir-ritonavir: 218, 23.98%; molnupiravir: 618, 28.14%), 1 event of hepatic impairment (nirmatrelvir-ritonavir: 0, 0%; molnupiravir: 1, 0.03%), 8 events of ischaemic stroke (nirmatrelvir-ritonavir: 3, 0.22%; molnupiravir: 5, 0.16%) and 9 events of myocardial infarction (nirmatrelvir-ritonavir: 2, 0.15%; molnupiravir: 7, 0.22%). Nirmatrelvir-ritonavir users had lower rates of all-cause mortality (absolute risk reduction (ARR) at 90 days 2.91%, 95% CI: 1.47-4.36%) and hospitalisation (ARR at 90 days 4.16%, 95% CI: 0.81-7.51%) as compared with molnupiravir users. Similar rates of ICU admission (ARR at 90 days-0.09%, 95% CI:-0.4 to 0.2%), ventilatory support (ARR at 90 days 0.13%, 95% CI:-0.45 to 0.72%), hepatic impairment (ARR at 90 days 0.03%, 95% CI:-0.03 to 0.09%), ischaemic stroke (ARR at 90 days-0.06%, 95% CI:-0.35 to 0.22%), and myocardial infarction (ARR at 90 days 0.07%, 95% CI:-0.19 to 0.33%) were found between nirmatrelvir-ritonavir and molnupiravir users. Consistent results were observed in relative risk adjusted with baseline characteristics. Nirmatrelvir-ritonavir was associated with significantly reduced risk of all-cause mortality (HR: 0.624, 95% CI: 0.455-0.857) and hospitalisation (HR: 0.782, 95% CI: 0.64-0.954). Patients with COVID-19 with advanced kidney disease receiving nirmatrelvir-ritonavir had a lower rate of all-cause mortality and hospital admission when compared with molnupiravir. Other adverse clinical outcomes were similar in both treatment groups. Health and Medical Research Fund (COVID1903010), Health Bureau, The Government of the Hong Kong Special Administrative Region, China.

Marginal zone lymphoma international prognostic index: a unifying prognostic index for marginal zone lymphomas requiring systemic treatment

Marginal zone lymphomas (MZL), comprised of three unique but related subtypes, lack a unifying prognostic score applicable to all the patients in need for systemic chemotherapy and/or immunotherapy. Patients from the prospective NF10 study (NCT02904577) with newly diagnosed MZL and receiving frontline systemic therapy at diagnosis or after observation were used to train a prognostic model. The primary endpoint was progression-free survival (PFS) from start of treatment. The model was externally validated in a pooled analysis of two independent cohorts from the University of Iowa and Mayo Clinic Molecular Epidemiology Resource and the University of Miami. We identified 501 eligible patients. After multivariable modeling, lactate dehydrogenase (LDH) above upper normal limit, hemoglobin <12g/dL, absolute lymphocyte count <1×109/L, platelets <100×109/L, and MZL subtype (nodal or disseminated) were independently associated with inferior PFS. The proposed MZL International Prognostic index (MZL-IPI) combined these 5 factors, and we defined low (LRG, 0 factors, 27%), intermediate (IRG, 1-2 factors, 57%) and high (HRG, 3+ factors, 16%) risk groups with 5-y PFS of 85%, 66%, and 37%, respectively (c-Harrell=0.64). Compared to the LRG, the IRG (Hazard Ratio [HR]=2.30, 95% CI 1.39-3.80) and HRG (HR=5.41, 95% CI 3.12-9.38) had inferior PFS. Applying the MZL-IPI to the pooled US cohort (N=353), 94 (27%), 192 (54%), and 67 (19%) patients were classified as LRG, IRG, and HRG, respectively, and the model was validated for PFS (log-rank test p=0.0018; c-Harrell=0.578, 95% CI 0.54-0.62). The MZL-IPI was also prognostic for OS in both the training and the external validation sets. MZL-IPI is a new prognostic score for use in all patients with MZL considered for systemic treatment. The MER was supported by P50 CA97274 and U01 CA195568.

Pharmacist-Led Deprescribing of Aspirin in Older People in an Outpatient Setting.

Background In 2019, the American College of Cardiology and American Heart Association updated their joint guidelines stating low-dose aspirin should not be used on a routine basis for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among people older than 70 years of age because of increased bleeding risk.1 In addition to these updated guidelines, a statement released by the US Preventive Services Task Force in April 2022 recommends against the initiation of low-dose aspirin for primary prevention of cardiovascular disease in people 60 years of age or older.² Despite these updated recommendations, aspirin continues to be a common medication older patients take, providing an opportunity for a clinical pharmacist deprescribing intervention. Objective To identify the role of a pharmacist-led aspirin deprescribing intervention within a safety-net health system in the outpatient setting. Methods This project included patients 70 years of age and older who had aspirin listed as an active medication without documented ASCVD. This project assessed aspirin deprescribing rates, time spent on pharmacist outreach, and reasons for patient and/or provider refusal to discontinue aspirin. Results One hundred thirty-one eligible patients were contacted. Of those, 78 (60%) patients discontinued aspirin after speaking with the pharmacist, and 8 patients discontinued aspirin after a clinical pharmacist recommendation to the patient's primary care provider (PCP). The median time spent on outreach was approximately eight minutes. Of the 6 patients who consented to the project but declined to discontinue aspirin therapy based on pharmacist intervention, 5 preferred to discuss the issue with their PCP, while 1 patient was told by an outside provider to take aspirin. Conclusion Results indicate the successful impact a clinical pharmacist may have in deprescribing aspirin in a high-risk population. These data may also suggest that an active and intentional approach to deprescribing is likely to be more effective than a written recommendation to providers.

Visual Outcome after Cataract Surgery in a South-Eastern Nigerian Tertiary Hospital

Background: Cataract is the leading cause of reversible blindness worldwide. Aim: To evaluate the visual outcome of cataract surgeries done in a South-Eastern tertiary hospital. Methodology: The study is a 2-year retrospective study from January 2021 to December 2022. Case notes of all eligible patients that had cataract surgery within the study period were pulled out and relevant information extracted from them. Collected data was analyzed using SPSS version 21. Results were presented in percentages, tables and pie charts. Results: One hundred and eighty-two eyes were analyzed. Visual outcome continued to improve postoperatively in majority of the patients from first day to 3 months and was even better in some when corrected with glasses or with pinhole. The overall visual outcome was good in 70.3% and poor in 10.4% at 3 months. The major causes of poor visual outcome were aphakia and advanced glaucoma. Conclusion: The overall visual outcome after cataract surgery in these patients did not meet the WHO standard. Thus, there is need for training and re-training of the cataract surgeons, good patients’ selection, in-depth pre-operative work up as well as centre-based provision of needed equipments/ consumables in other to improve the visual outcome.

Serial neutrophils count as a stratifying tool for early follicular tonsilitis remission

Background/Aim: This study examines the correlation between sequential serum neutrophil levels and the overall improvement status or reduction rate of intravenous antibiotic administration. This study seeks to identify a cost-effective and easily accessible biomarker that can accurately predict the need for hospitalisation in patients with acute tonsillitis who are receiving intravenous broad-spectrum antibiotics. The goal is to determine the patients' suitability for early discontinuation of intravenous antibiotics and discharge. Methods: This study was conducted at the King Hussein Medical Centre in Jordan, focusing on patients with severe acute tonsillitis who did not respond to oral antibiotics. Data was collected from the electronic medical record system (Hakeem) from January 2018 to May 2021. The study classified serial serum neutrophil measurements during the first week of hospital admission into four categories. The levels were compared between the non-penicillin Cohort (Group I) and penicillin Cohort (Group II) using an Independent-T Test. The outcomes of interest included a drop in neutrophil counts exceeding 50%, a decrease in the use of intravenous antibiotics in favor of oral antibiotics, and early eligibility for discharge. The study also examined serial neutrophil counts over the tested days and compared to the outcomes of positive and negative states using receiver operating curve analyses. The optimal cutoff operating point for each ROC curve was determined by selecting the highest Youden's index of each prognosticator day level. The analysis of all results was conducted using SPSS version 20 with a significance level set at p-value &lt;0.05. Results: This study analyzed 1638 adult and elderly patients admitted to KHMC, RMS, Amman, Jordan between January 2018 and May 2021. The average age was 51.88±16.22 years, with patients dependent on intravenous penicillin being slightly older. The distribution of males and females was significant, with males making up 2.55 times the number of females. The odds ratio for positive outcomes was 4.12, with a high rate of poor outcomes in 1318 out of all eligible patients. A total of 994 (60.7%) medical patients were treated with intravenous administration, while 644 (39.3%) surgical patients were scheduled for a tonsillectomy procedure. The risk estimate for patients admitted from medical wards compared to surgical wards was an odds ratio of 0.562. The study also provided sensitivity analysis for the four tested serial neutrophil prognosticators at different day levels. Conclusion: The study supports the use of Somatic Nucleated Cell (SNC) as a reliable measure for evaluating EFR in cases of catarrhal acute tonsillitis. The maximum SNC count in Group one was 11,269 cells per cubic millimeter. Acute streptococcal infection often exhibits an ESR higher than 40, but this may be concealed by other complications. The SNC test has advantages like simplicity, quickness, and cost-effectiveness, but lacks specificity. Monitoring SNC and EFR fluctuations can initiate treatment cessation, preventing relapse and severe complications during recovery.

Progressive pulmonary fibrosis (PPF): Estimation of incidence and treatment rates in Japan using a claims database

BackgroundInterstitial lung diseases (ILDs) are a heterogeneous group of disorders, a subset of which develop progressive pulmonary fibrosis (PPF). There is little information on the epidemiology and treatment of PPFs in Japan. This retrospective cohort study estimated the incidence probability of progression to PPFs in patients with fibrosing ILDs other than idiopathic pulmonary fibrosis in a real-world Japanese setting. Management procedures and treatment patterns were also quantified. MethodsData were extracted from the Medical Data Vision database from 01-Jan-2012 to 28-May-2020, comprising a 6.91-year patient identification period, 1-year pre-index period, and post-index period. The primary outcome was the cumulative incidence probability of progression to PPF up to 24 months. Subgroup analyses were performed by the presence/absence of connective tissue disease-ILD and by pre-specified ILD clinical diagnosis. ResultsOf the 34,960 eligible patients (mean age: 71.1 years, males: 52.5%), 14,580 (41.7%) progressed to PPF. The 24-month incidence probability of progression to PPF was 39.5%. A relatively comparable percentage of patients progressed across all ILD subtypes. Oral corticosteroids and tacrolimus were the most common therapies during the pre- and post-index periods. Treatment rates were very low in the post-index period. ConclusionsThis is the first claims database study to estimate the incidence probability of progression to PPF in Japan. Progression appeared common in patients with chronic fibrosing ILDs, with comparable percentages of patients across all subtypes developing PPF at 2 years. Future studies should assess the impact of regular monitoring and early intervention on treating fibrotic ILDs and preventing progression.

Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia.

Angiopoietin-like 3 (ANGPTL3) inhibits lipoprotein and endothelial lipases and hepatic uptake of triglyceride-rich lipoprotein remnants. ANGPTL3 loss-of-function carriers have lower levels of triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol and a lower risk of atherosclerotic cardiovascular disease than noncarriers. Zodasiran is an RNA interference (RNAi) therapy targeting expression of ANGPTL3 in the liver. We conducted a double-blind, placebo-controlled, dose-ranging phase 2b trial to evaluate the safety and efficacy of zodasiran in adults with mixed hyperlipidemia (fasting triglyceride level of 150 to 499 mg per deciliter and either an LDL cholesterol level of ≥70 mg per deciliter or a non-HDL cholesterol level of ≥100 mg per deciliter). Eligible patients were randomly assigned in a 3:1 ratio to receive subcutaneous injections of zodasiran (50, 100, or 200 mg) or placebo on day 1 and week 12 and were followed through week 36. The primary end point was the percent change in the triglyceride level from baseline to week 24. A total of 204 patients underwent randomization. At week 24, substantial mean dose-dependent decreases from baseline in ANGPTL3 levels were observed with zodasiran (difference in change vs. placebo, -54 percentage points with 50 mg, -70 percentage points with 100 mg, and -74 percentage points with 200 mg), and significant dose-dependent decreases in triglyceride levels were observed (difference in change vs. placebo, -51 percentage points, -57 percentage points, and -63 percentage points, respectively) (P<0.001 for all comparisons). Other differences in change from baseline as compared with placebo included the following: for non-HDL cholesterol level, -29 percentage points with 50 mg, -29 percentage points with 100 mg, and -36 percentage points with 200 mg; for apolipoprotein B level, -19 percentage points, -15 percentage points, and -22 percentage points, respectively; and for LDL cholesterol level, -16 percentage points, -14 percentage points, and -20 percentage points, respectively. We observed a transient elevation in glycated hemoglobin levels in patients with preexisting diabetes who received the highest dose of zodasiran. In patients with mixed hyperlipidemia, zodasiran was associated with significant decreases in triglyceride levels at 24 weeks. (Funded by Arrowhead Pharmaceuticals; ARCHES-2 ClinicalTrials.gov number, NCT04832971.).

Diabetes and further risk of cancer: a nationwide population-based study

BackgroundIndividuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood.MethodsThis was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period.ResultsWe observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001).ConclusionsThis study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops.

Sustained increase in annual transcranial Doppler screening rates in children with sickle cell disease: A quality improvement project.

Individuals with sickle cell disease (SCD) at increased risk for stroke should undergo annual stroke risk assessment using transcranial Doppler (TCD) screening between the ages of 2 and 16. Though this screening can significantly reduce morbidity associated with SCD, screening rates at Boston Children's Hospital (and nationwide) remain below the recommended 100% screening adherence rates. Three plan-do-study-act (PDSA) cycles were designed and implemented. The Specific, Measurable, Achievable, Relevant, and Time-Bound (SMART) aim of our quality improvement (QI) initiative was to sustainably increase the proportion of eligible patients receiving a TCD within 15months of their last TCD to greater than 95%. An interrupted time series (ITS) analysis was performed, comparing TCD adherence rates from PDSA Cycle 1 to those from PDSA Cycles 2 and 3. Mean TCD adherence increased across all three PDSA cycles, from a baseline of 67% in the first cycle (January 2015 to September 2020) to 92% in the third cycle (May 2021 to March 2023). In the ITS analysis of TCD adherence rates, there was a significant difference in the final TCD adherence rate achieved compared to the rate predicted, with a total estimated increase in adherence of 17.9% being attributable to the interventions from PDSA Cycles 2 and 3. Although other QI initiatives had demonstrated ability to increase adherence to TCD screening for patients with SCD, this is the first QI project to collect data over such a prolonged period of time to demonstrate a sustained increase in screening rates throughout the intervention (an 8-year period).

Influence of cerebrospinal fluid drainage in the first days after aneurysm rupture on the severity of early brain injury following aneurysmal subarachnoid hemorrhage

PurposeProgressive cerebral edema with refractory intracranial hypertension (ICP) requiring decompressive hemicraniectomy (DHC) is a severe manifestation of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH). The purpose of the study was to investigate whether a more pronounced cerebrospinal fluid (CSF) drainage has an influence on cerebral perfusion pressure (CPP) and the extent of EBI after aSAH.MethodsPatients with aSAH and indication for ICP-monitoring admitted to our center between 2012 and 2020 were retrospectively included. EBI was categorized based on intracranial blood burden, persistent loss of consciousness, and SEBES (Subarachnoid Hemorrhage Early Brain Edema Score) score on the third day after ictus. The draining CSF and vital signs such as ICP and CPP were documented daily.Results90 out of 324 eligible aSAH patients (28%) were included. The mean age was 54.2 ± 11.9 years. DHC was performed in 24% (22/90) of patients. Mean CSF drainage within 72 h after ictus was 168.5 ± 78.5 ml. A higher CSF drainage within 72 h after ictus correlated with a less severe EBI and a less frequent need for DHC (r=-0.33, p = 0.001) and with a higher mean CPP on day 3 after ictus (r = 0.2351, p = 0.02).ConclusionA more pronounced CSF drainage in the first 3 days of aSAH was associated with higher CPP and a less severe course of EBI and required less frequently a DHC. These results support the hypothesis that an early and pronounced CSF drainage may facilitate blood clearance and positively influence the course of EBI.

Counterpoint: In-Home Pulmonary Rehabilitation Is an Attractive Alternative.

Center-based pulmonary rehabilitation is positioned as the accepted standard for pulmonary rehabilitation. There, however, are several barriers to its utilization, and usage rates remain as low as 4%, despite decades of trying to improve access. The question then arises as to who is really benefiting from center-based pulmonary rehabilitation as this therapy is barely available to eligible patients. Alternative modes of delivery of pulmonary rehabilitation have been tested. Meta-analyses indicate that these alternate modes are associated with clinical improvements comparable with center-based pulmonary rehabilitation in several outcomes that are important for patients, including the 6-min walk distance, dyspnea, and quality of life. These modes are also associated with better adherence to the intervention than center-based pulmonary rehabilitation. Telehealth pulmonary rehabilitation and home-based pulmonary rehabilitation, therefore, are attractive alternatives to center-based pulmonary rehabilitation and will exponentially increase pulmonary rehabilitation capacity.

Optimal use of antithrombotic agents in recent small subcortical strokes accompanied by atrial fibrillation.

This study aimed to evaluate the efficacy and safety of anticoagulants (AC) and antiplatelets (APT) in patients with recent small subcortical infarctions (RSSI) and atrial fibrillation (AF). We utilized a prospective multicenter stroke registry database to identify patients with RSSI with a concurrent diagnosis of AF. Propensity score matching analysis was used to balance baseline differences among the AC-only, APT-only, and their combination groups. The main outcomes of interest were time to occurrence of minor and major bleeding, stroke recurrence, and all-cause mortality. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for each outcome were calculated using the multivariable Cox proportional hazard regression analysis. Of the 404 eligible patients, 28.2% received APT only, 53.0% received AC only, and 18.9% received a combination of both. Notable differences were observed between these groups in terms of the 1-year stroke recurrence (APT, 32.5%; AC, 5.6%; APT + AC, 9.2%) and all-cause mortality (APT, 21.9%; AC, 6.1%; APT + AC, 14.5%), whereas the rates of bleeding events were comparable. The multivariable analysis indicated a significant association of AC alone with reduced risks of severe bleeding, stroke recurrence, and all-cause mortality compared with APT alone (aHR 0.64, 95% CI 0.41-0.98; aHR 0.11, 95% CI 0.06-0.22; aHR 0.22, 95% CI 0.11-0.44, respectively). The combination group showed a reduced risk of stroke recurrence compared to APT alone (aHR 0.19, 95% CI 0.08-0.46). These findings remained consistent with the propensity score-matched analysis. AC showed better clinical outcomes than APT in patients with RSSI and AF. Additionally, combination therapy with AC and APT was associated with a lower risk of stroke recurrence than APT alone.

Predictive value of monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) for poor prognosis after intravenous thrombolytic therapy for acute ischaemic stroke

IntroductionThe purpose of this study was to examine the relationship between monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) and poor short-term 3-month and long-term 6-month prognosis after intravenous thrombolysis in patients with acute ischaemic stroke.Material and methodsBy retrospective analysis, 763 eligible patients with acute ischaemic stroke with intravenous thrombolysis were included in the study, and the general data and clinical laboratory examination results of the patients were collected. The relationship between MHR and poor prognosis at 3 and 6 months in patients with intravenous thrombolysis was derived by stepwise regression using the R language, followed by 1:1 propensity score matching to determine the MHR threshold and to investigate the relationship between high and low MHR values and poor prognosis.ResultsMHR level was found to predict the prognosis of intravenous thrombolysis patients with acute ischaemic stroke, and it was an effective predictor of poor prognosis at 3 and 6 months after intravenous thrombolysis. MHR has a threshold of 0.584. High MHR levels were strongly associated with a poor 3-month prognosis of intravenous thrombolysis in patients with acute ischaemic stroke (OR = 5.657; 95% CI: 4.124–7.762; p &lt; 0.001). High MHR level was closely associated with poor prognosis of acute ischaemic stroke patients with intravenous thrombolysis at 6 months (OR = 4.923; 95% CI: 3.603–6.726; p &lt; 0.001).ConclusionsMHR level is a valid predictor for poor prognosis at 3-6 months after intravenous thrombolysis in patients in acute ischaemic stroke.

Sex Differences in the Dual Antiplatelet Therapy Versus Alteplase for Patients with Minor Nondisabling Acute Ischemic Stroke: A Secondary Analysis of the ARAMIS Study.

Sex is associated with clinical outcome in stroke. The present study aimed to determine the effect of sex on efficacy of dual antiplatelet (DAPT) versus alteplase in ischemic stroke based on Antiplatelet versus recombinant tissue plasminogen activator (R-tPA) for Acute Mild Ischemic Stroke (ARAMIS) trial. In this secondary analysis of the ARAMIS study, eligible patients aged 18 years or older with minor nondisabling stroke who received dual antiplatelet therapy or intravenous alteplase within 4.5 h of stroke onset were divided into two groups: men and women. The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale (mRS) 0-1 at 90 days. Binary logistic regression analyses and generalized linear models were used. Of the 719 patients who completed the study, 31% (223) were women, and 69% (496) were men. There were no significant sex differences in excellent functional outcome (unadjusted p = 0.304 for men and p = 0.993 for women; adjusted p = 0.376 for men and p = 0.918 for women) and favorable functional outcome (mRS score of 0-2; unadjusted p = 0.968 for men and p = 0.881 for women; adjusted p = 0.824 for men and p = 0.881 for women). But for the secondary outcomes, compared with alteplase, DAPT was associated with a significantly decreased proportion of early neurological deterioration within 24 h in men {unadjusted odds ratio [OR] = 0.440 [95% confidence interval (CI), 0.221-0.878]; p = 0.020; adjusted OR = 0.436 [95% CI, 0.216-0.877]; p = 0.020}, but not in women [unadjusted OR = 0.636 (95% CI, 0.175-2.319), p = 0.490; adjusted OR = 0.687 (95% CI, 0.181-2.609), p = 0.581]. For the safety outcomes, compared with the DAPT group, alteplase was associated with a significantly increased proportion of any bleeding events in men [unadjusted OR = 3.110 (95% CI, 1.103-8.770); p = 0.032], but not in women [unadjusted OR = 5.333 (95% CI, 0.613-46.407), p = 0.129; adjusted OR = 5.394 (95% CI, 0.592-49.112), p = 0.135]. Sex did not influence the effect of dual antiplatelet therapy versus intravenous alteplase in minor nondisabling stroke, but more early neurological deterioration and bleeding events occurred in men who received alteplase.

Incidence, Predictors, and Implications of Secondary Aortic Intervention Following Thoracic Endovascular Aortic Repair for Type B Dissection.

Secondary aortic intervention (SAI) following thoracic endovascular aortic repair (TEVAR) is not uncommon. However, a satisfactory management system has not been established for these patients. We aimed to report our single-center experience with SAI after prior TEVAR for type B aortic dissection (TBAD). From January 2010 to May 2017, 860 eligible patients with TBAD underwent TEVAR. One hundred seven (12.4%) patients required SAI, either endovascularly (n=76) or surgically (n=31). The main indications for SAI were entry flow (n=58 [54.2%]), aneurysm expansion of the proximal or remote aorta (n=26 [24.3%]), retrograde type A aortic dissection (n=11 [10.3%]), distal stent-graft-induced new entry tear (n=6 [5.6%]), and stent migration (n=4 [3.7%]). The Kaplan-Meier curves were generated to determine the degree of freedom from SAI and the prognosis. Cox proportional hazards were used to screen for risk factors for SAI and poor prognosis. The overall 30-day mortality rate after SAI was 4.7% (n=5): endovascular (n=2 [2.6%]) vs open surgery (n=3 [9.7%]; p=0.145). The cumulative survival rates with or without SAI were 86.3%±3.6% vs 95.7%±0.8% at 3 years and 82.0%±4.2% vs 92.2%±1.1% at 5 years, respectively (log-rank p<0.001). Although no significant difference in survival was observed, the incidence of SAI was significantly greater in patients who underwent TEVAR during the chronic phase (acute [11.6%] vs subacute [9.6%] vs chronic [27.8]; p<0.001). Multivariate regression analysis revealed that prior TEVAR in the chronic phase (hazard ratio [HR]=1.73, 95% confidence interval [CI]=1.03-2.90; p=0.039), maximum aortic diameter (HR=1.05, 95% CI=1.04-1.07; p<0.001), and arch involvement (HR=1.48, 95% CI=1.01-2.18; p=0.048) were predictors of the incidence of SAI. In addition, the maximum aortic diameter was demonstrated to be the only risk factor for prognosis after adjusting for confounding factors. Thoracic endovascular aortic repair for chronic TBAD patients should be reconsidered. Open surgery is preferable for those with proximal progression, whereas endovascular treatment is more suitable for distal lesions. Close surveillance and timely reintervention after TEVAR, whether via endovascular techniques or open surgery, are necessary to prevent devastating complications. The management of patients with type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR) is challenging. We summarized our single-center experience regarding secondary aortic intervention after TEVAR for TBAD. We found that TEVAR for chronic TBAD patients should be carefully evaulated, and open surgery is recommended for those with proximal progession, while endovascular treatment is more preferable for distal lesions.