Primary Outcome Research Articles

Utilization and safety of off-label prothrombin complex concentrate (4F-PCC) in a nonsurgical population.

The aim of this study was to evaluate and describe the utilization and safety of 4F-PCC in a nonanticoagulated, nonsurgical patient population at an academic, tertiary care center. This retrospective, single-center chart review evaluated nonanticoagulated adult patients at least 18 years of age who had at least one dose of 4F-PCC administered between January 1, 2017, and September 30, 2022, for a nonsurgical indication. Hemostatic efficacy following 4F-PCC administration was the primary outcome, and secondary outcomes included an assessment of blood product administration, thrombotic events within 30 days post4F-PCC administration, in-hospital mortality, and the length of hospital stay. A total of 59 patients met the inclusion criteria, and 10 patients received 4F-PCC for coagulopathy associated with liver disease, 34 for intracranial hemorrhage (ICH), and 15 for other indications. For the primary outcome of hemostatic efficacy, 17 non-ICH patients (85%) had achieved hemostasis post-4F-PCC, and among the ICH patient population, 18 (64%) did not show expansion on repeat CT post4F-PCC, suggesting hemostasis. Blood product and hemostatic agent usage was frequent, with 72.9% of patients requiring products post-4F-PCC. Acute thromboembolic events occurred in six patients (10.2%), and in-hospital mortality occurred in 55.9% of patients. Off-label 4F-PCC use is common despite a lack of robust guidance for use. Following 4F-PCC administration, blood product use was frequent, the incidence of in-hospital mortality was high, and thromboembolic complications such deep vein thrombosis (DVT), pulmonary embolism (PE), and stroke were reported. Further studies are needed to validate the off-label administration of 4F-PCC in nonanticoagulated patients.

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.

Real-world Impact of 3 and 4.5 mg Doses of Dulaglutide on Weight and Hemoglobin A1c in Patients With Type 2 Diabetes Mellitus.

Limited real-world data on the benefits and risks associated with 3 and 4.5 mg doses of dulaglutide currently exists, making it difficult to determine the impact of dose titration for patients currently managed with dulaglutide 1.5 mg weekly. To determine the impact of dulaglutide 3 and 4.5 mg doses on weight and hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM), in clinical practice. Retrospective, observational study of adult T2DM patients receiving dulaglutide 3 or 4.5 mg weekly within a large, university-affiliated, primary care network. The primary outcome was change in weight and HbA1c from baseline to 24 weeks. Secondary outcomes included incremental changes in weight and HbA1c, and describing trends related to dose reductions. Ninety-five patients were included, 62 in the dulaglutide 3 mg group and 33 in the dulaglutide 4.5 mg group. After 24 weeks, the mean changes in weight and HbA1c from baseline were -1.8 kg (P < 0.01) and -0.4% (P < 0.01) in the 3 mg group, and -4.2 kg (P < 0.01) and -0.4% (P = 0.119) in the 4.5 mg group. Incremental change in weight and HbA1c among patients who were titrated from dulaglutide 3 to 4.5 mg weekly were -2.6 kg (P < 0.01) and -0.2% (P = 0.04), respectively. Titration from dulaglutide 1.5 to 3 mg resulted in significant reductions in weight and HbA1c after 24 weeks. Additional, statistically significant, reductions in weight and HbA1c were seen when patients were further titrated to dulaglutide 4.5 mg weekly.

A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

Outcomes by sex in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial.

In the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial, among participants with stable coronary artery disease, the risk of cardiac events was similar between an invasive (INV) strategy of angiography and coronary revascularisation and a conservative (CON) strategy of initial medical therapy alone. Outcomes according to participant sex were not reported. We aimed to analyse the outcomes of ISCHEMIA by participant sex. We evaluated 1) the association between participant sex and the likelihood of undergoing revascularisation for participants randomised to the INV arm; 2) the risk of the ISCHEMIA primary composite outcome (cardiovascular death, any myocardial infarction [MI] or rehospitalisation for unstable angina, heart failure or resuscitated cardiac arrest) by participant sex; and 3) the contribution of the individual primary outcome components to the composite outcome by participant sex. Of 5,179 randomised participants, 1,168 (22.6%) were women. Female sex was independently associated with a lower likelihood of revascularisation when assigned to the INV arm (adjusted odds ratio 0.75, 95% confidence interval [CI]: 0.57-0.99; p=0.04). The INV versus CON effect on the primary composite outcome was similar between sexes (women: hazard ratio [HR] 0.96, 95% CI: 0.70-1.33; men: HR 0.90, 95% CI: 0.76-1.07; pinteraction=0.71). The contribution of the individual components to the composite outcome was similar between sexes except for procedural MI, which was significantly lower in women (9/151 [5.9%]) than men (67/519 [12.9%]; p=0.01). In ISCHEMIA, women assigned to the INV arm were less likely to undergo revascularisation than men. The effect of an INV versus CON strategy was consistent by sex, but women had a significantly lower contribution of procedural MI to the primary outcome.

Effects of an eight-week physical exercise program on low back pain and function in fruit workers: A randomized controlled trial.

Low back pain is prevalent in workers' health and functional performance. To evaluate the effects of a physical exercise program on low back pain and disability in fruit workers. This randomized controlled trial assigned 44workers (37 ± 9years) to two groups. The experimental group consisted of 10men and 12women with an average age of 38 (± 9) years, and the control group consisted of 8men and 14women with an average age of 36 (± 10) years. The experimental group (EG) performed a program of strength and flexibility exercises for eight weeks, twice a week. The control group (CG) received minimal care, with a booklet with guidelines for performing exercises. The primary outcomes included changes in perceived disability and the intensity of pain evaluated by the Rolland-Morris questionnaire and the Numerical Pain Scale, respectively. All outcomes were measured at baseline and after eight weeks of intervention. A significant difference was observed in the within-group analysis, with a mean reduction in pain intensity in the EG and CG of -4.55 (95%CI -7.01 to -2.09) and -3.81 (95%CI 1.72-5.90), respectively. For disability, a reduction of -4.45 (95% CI -8.89 to -0.02) was observed in the EG and of -4.43 (-7.38 to -1.48) in the CG. There were no significant differences in the between-groups analysis. The exercise program was not superior to using the educational booklet. However, both interventions showed substantial decreases in pain and disability levels.

The clinical outcomes and effectiveness of antiviral agents among underweight patients with COVID-19

ABSTRACT Objectives This study investigated the outcomes ofunderweight patients with COVID-19 and the effectiveness of antiviral agents inthis population. Methods A retrospective cohort study using theTriNetX research network wasconducted. Propensity score matching (PSM) was employed to balance the firstcohort involving COVID-19 patients with underweight and normal-weight. In thesecond cohort, underweight patients receiving antiviral agents and untreatedindividuals were matched using PSM. The primary outcome was a composite ofall-cause hospitalization and death during the 7–30-day follow-up period. Results After PSM, the first cohort including eachgroup of 13,502 patients with balanced baseline characteristics were identifiedfor comparing the outcome of patients with underweight and normal weight. The underweightgroup had a higher risk of the composite primary outcome than those with normalweight (hazard ratio [HR], 1.251; 95% confidence interval [CI], 1.132–1.382). The second cohort included each 884 underweight patients withand without receiving antivirals.Compared with untreated patients,those receiving antiviral treatment had a lower risk of composite primaryoutcomes (HR, 0.426; 95% CI, 0.278–0.653). Conclusion Underweight status may be associated with ahigher risk of all-cause hospitalization and death in patients with COVID-19.Among underweight patients, antiviral agents demonstrated clinically beneficial effects.

The Device for Intraventricular Entry guide: a novel solution to a perpetual problem.

The authors designed a low-profile device for reliable ventricular access and prospectively studied its safety, efficacy, and accuracy at a large academic center. A novel device for ventricular entry, the Device for Intraventricular Entry (DIVE) guide, was designed and created by the first and senior authors. Fifty patients undergoing external ventricular drainage (EVD) or shunt placement were prospectively enrolled for DIVE-assisted catheter placement at a single academic center. The primary outcome was the catheter tip location on postprocedural CT. Secondary outcomes included number of catheter passes, clinically significant hemorrhages, and procedure-related infections. Fifty patients were enrolled. Indications included subarachnoid hemorrhage, intraventricular hemorrhage, traumatic brain injury, hydrocephalus, pseudotumor, and postsurgical wound drainage. In total, 76% (38/50) of patients underwent right-sided placement and 24% (12/50) underwent left-sided placement. All 100% (50/50) of patients had successful cannulation with an average of 1.06 passes. Postprocedural head CT confirmed ipsilateral frontal horn or third ventricle placement (Kakarla grade 1) in 92% (46/50) of patients and placement in the contralateral lateral ventricle in 8% (4/50) (Kakarla grade 2). There were no clinically significant track hemorrhages or procedural infections. This single-center prospective study investigated the safety and efficacy of DIVE-assisted ventricular access. In total, 100% of procedures had successful ventricular cannulation, with 92% achieving Kakarla grade 1, with an average of 1.06 passes without any clinical complications.

Revisiting Cardiovascular Benefits of Blood Pressure Reduction in Primary and Secondary Prevention: Focus on Targets and Residual Risk-A Systematic Review and Meta-Analysis.

Previous meta-analyses resurrected the debated statement "the lower, the better" following blood pressure (BP)-lowering treatment. We investigated the benefits of BP-lowering treatment at different BP targets by prevention category. The meta-analysis protocol was registered at the International Prospective Register of Systematic Reviews (CRD42022379249). The database included 115 BP-lowering or comparison trials from patients with (n=241 089) or without (n=198 937) previous cardiovascular events. Prevention disease groups were stratified by in-treatment achieved BP, drug class versus placebo, and drug class versus other classes. Risk ratios and 95% CIs of major adverse cardiovascular events were calculated. Following a standard (10/5 mm Hg) BP reduction, major adverse cardiovascular event relative risk reductions were not different between prevention groups (primary, 25% [95% CI, 18%-31%]; secondary, 28% [95% CI, 20%-37%]). For achieved systolic BP of at least 140 mm Hg, between 130 and 140 mm Hg, and <130 mm Hg (nadir, 125 mm Hg), (1) risk ratios of major adverse cardiovascular events and absolute risk reductions were not different between prevention groups across systolic BP strata, and (2) residual risk, though 4.1× greater in secondary than primary prevention, decreased in primary prevention from higher to lower systolic BP targets. The effect of separate drugs versus others on the primary outcome was not different between prevention groups. BP-lowering treatment benefits did not differ by prevention group to a nadir of 125 mm Hg for systolic BP. Although residual risk in secondary prevention is higher than in primary prevention, it gradually decreases at progressively lower systolic BP targets in primary prevention. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42022379249.

Effects of Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic Review and Meta-analysis.

The aim of this study was to summarize the optimal strategy for early feeding in patients with acute pancreatitis. The search was undertaken in electronic databases, which compared early with delayed feeding in acute pancreatitis. The primary outcome was the length of hospital stay (LOHS). The second outcomes were intolerance of refeeding, mortality, and total cost of each patient. This meta-analysis followed the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guideline. Research is registered by PROSPERO, CRD42020192133. A total of 20 trials involving 2168 patients were included, randomly assigned to the early feeding group (N = 1033) and delayed feeding group (N = 1135). The LOHS was significantly lower in the early feeding group than the delayed feeding group (mean difference: -2.35, 95% CI: -2.89 to -1.80; P < 0.0001), no matter the mild or severe subgroup ( Pint = 0.69). The secondary outcome of feeding intolerance and mortality were no significant difference (risk ratio: 0.96, 0.40 to 2.16, P = 0.87 and 0.91, 0.57 to 1.46, P = 0.69; respectively). Moreover, the hospitalization cost was significantly less in the early feeding group, resulting in an average savings of 50%. In patients with severe pancreatitis, early feeding after 24 hours may be beneficial ( Pint = 0.001). Early oral feeding can significantly reduce the LOHS and hospitalization costs in patients with acute pancreatitis without increasing feeding intolerance or mortality. In patients with severe pancreatitis, early feeding after 24 hours may be beneficial.

Orbital reconstruction and volume in the correction of proptosis after resection of spheno-orbital meningiomas.

The objective of this study was to evaluate the effect of reconstruction and orbital volume on the reduction of proptosis in patients undergoing resection for spheno-orbital meningiomas. Additionally, potential predictors of optimal proptosis reduction after surgery were evaluated. Patients with spheno-orbital meningiomas who underwent resection at the authors' institution between 2005 and 2020 were evaluated retrospectively. The exophthalmos index (EI) was measured on pre- and postoperative imaging to quantify proptosis and calculate the primary outcome measure of proptosis reduction. Patients were excluded if they had no preoperative proptosis (i.e., EI < 1.1), prior resection, or insufficient imaging available for analysis. Clinical and surgical characteristics were collected, including sex, extent of resection, WHO grade, and rigid orbital reconstruction, and assessed as predictors of greater proptosis reduction. Additionally, orbital volumes of the affected and contralateral orbits were measured to correlate postoperative orbital volumes with proptosis reduction. Thirty-three patients, with a mean age of 53 years, met inclusion criteria. The majority of the patients were female (23, 69.7%), and most tumors were classified as WHO grade 1 (29, 87.9%). Six patients (18.2%) underwent rigid orbital reconstruction. The mean EI across all patients decreased from 1.36 ± 0.18 to 1.19 ± 0.15 (p < 0.001). Patients who underwent reconstruction had on average a 76.4% greater reduction in the EI (p = 0.036) and a 9.1 times higher odds of achieving a normal EI (< 1.1) compared with those who did not receive reconstruction (OR 9.1, p = 0.025). Additionally, patients without residual hyperostotic bone compressing the orbit had a 2.16 times greater reduction in EI (p = 0.039). A linear relationship between orbital volume ratios (affected/unaffected orbit) and proptosis reduction was observed (p = 0.029, r = 0.529), including at ratios > 1.0. This suggests that greater orbital volumes postoperatively correlated with greater reductions in proptosis. Three factors were identified that optimize proptosis correction. First, all abnormal bone compressing the orbital contents must be removed completely. Second, rigid orbital reconstruction leads to improved proptosis correction, possibly by preventing frontal lobe and dural reconstruction from descending onto the compressed orbit. Third, aiming for an orbital volume slightly larger than the contralateral normal side leads to improved proptosis correction.

Effect of delayed hospitalization on 3-year clinical outcomes according to renal function in patients with non-ST-segment elevation myocardial infarction.

We evaluated the effect of delayed hospitalization (symptom-to-door time [STD] ≥ 24 h) on 3-year clinical outcomes according to renal function in patients with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing new-generation drug-eluting stent (DES) implantation. A total of 4513 patients with NSTEMI were classified into chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m², n = 1118) and non-CKD (eGFR ≥ 60 mL/min/1.73 m², n = 3395) groups. They were further sub-classified into groups with (STD ≥ 24 h) and without (STD < 24 h) delayed hospitalization. The primary outcome was the occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction, any repeat coronary revascularization, and stroke. The secondary outcome was stent thrombosis (ST). After multivariable-adjusted and propensity score analyses, the primary and secondary clinical outcomes were similar in patients with or without delayed hospitalization in both CKD and non-CKD groups. However, in both the STD < 24 h and STD ≥ 24 h groups, MACCE (p < 0.001 and p < 0.006, respectively) and mortality rates were significantly higher in the CKD group than in the non-CKD group. However, ST rates were similar between the CKD and non-CKD groups and between the STD < 24 h and STD ≥ 24 h groups. Chronic kidney disease appears to be a much more important determinant of MACCE and mortality rates than STD in patients with NSTEMI.

Quantifying Head Position Following Vitrectomy Using a 3-Dimensional Position Sensor Embedded in a Novel Ophthalmic Shield: A Pilot Study.

To assess head position following pars plana vitrectomy (PPV) using a novel low-energy, non-intrusive 3-D position sensor platform. In this prospective non-randomized interventional case series, a low-energy Bluetooth smart sensor housed within a novel eye shield recorded 3-D positional data every five minutes. The device was placed on the patient immediately after PPV and data was retrieved at the postoperative day 1 visit. Readings were processed by vector analysis into 4 groups, stratified by the angle of deviation away from a completely prone head position. The primary outcome was the angle between vectors. Ten patients were enrolled in this pilot study. The mean (SD) age was 57.5 (17.4). A total of 2318 readings with a mean (SD) of 231.8 (26.8) readings per patient were obtained. The mean (SD) number of readings were 132.9 (34.7) while awake and 98.9 (27.9) during sleep. Of total readings, only 11.7% fell into group 1 while a majority of readings fell in group 2 (52.4%), and group 3 (32.4%), and only 3.5% fell into group 4. Positional deviation increased during sleep hours, with about 46.8% of readings at a reclined angle (group 3) and 4.9% supine, which was 21.6% and 2.5% respectively during the wake time (p<0.001, p=0.002, respectively). In this pilot study, a non-intrusive wireless 3-D position sensor-shield platform was tolerated well and capable of capturing positional data. Adherence to face-down positioning was low and positional deviation increased significantly while sleeping.

Recent outcomes of surgical redo aortic valve replacement in prosthetic valve failure.

As redo surgical aortic valve replacement(AVR) is relatively high risk, valve-in-valve transcatheter AVR has emerged as an alternative for failed prostheses. However, the majority of studies are outdated. This study assessed the current clinical outcomes of redo AVR. This study enrolled 324 patients who underwent redo AVR due to prosthetic valve failure from 2010 to 2021 in four tertiary centers. The primary outcome was operative mortality. The secondary outcomes were overall survival, cardiac death, and aortic valve-related events. Logistic regression analysis, clustered Cox proportional hazards models, and competing risk analysis were used to evaluate the independent risk factors. Redo AVR was performed in 242 patients without endocarditis and 82 patients with endocarditis. Overall operative mortality was 4.6% (15 deaths). Excluding patients with endocarditis, the operative mortality of redo AVR decreased to 2.5%. Multivariate analyses demonstrated that endocarditis (HR 3.990, P=0.014), longer cardiopulmonary bypass time (HR 1.006, P=0.037) and lower left ventricular ejection fraction (LVEF) (HR 0.956, P=0.034) were risk factors of operative mortality. Endocarditis and lower LVEF were independent predictors of overall survival. The relatively high risk of redo AVR was due to reoperation for prosthetic valve endocarditis. The outcomes of redo AVR for non-endocarditis are excellent. Our findings suggest that patients without endocarditis, especially with acceptable LVEF, can be treated safely with redo AVR.

Maternal Morbidity According to Mode of Delivery Among Pregnant Patients With Pulmonary Hypertension.

Patients with pulmonary hypertension have a high risk of maternal morbidity and mortality. It is unknown if a trial of labor carries a lower risk of morbidity in these patients compared to a planned cesarean delivery. The objective of this study was to examine the association of delivery mode with severe maternal morbidity events during delivery hospitalization among patients with pulmonary hypertension. This retrospective cohort study used the Premier inpatient administrative database. Patients delivering ≥25 weeks gestation from January 1, 2016, to September 30, 2020, and with pulmonary hypertension were included. The primary analysis compared intended vaginal delivery (ie, trial of labor) to intended cesarean delivery (intention to treat analysis). A sensitivity analysis was conducted comparing vaginal delivery to cesarean delivery (as treated analysis). The primary outcome was nontransfusion severe maternal morbidity during the delivery hospitalization. Secondary outcomes included blood transfusion (4 or more units) and readmission to the delivery hospital within 90 days from discharge from delivery hospitalization. The cohort consisted of 727 deliveries. In the primary analysis, there was no difference in nontransfusion morbidity between intended vaginal delivery and intended cesarean delivery groups (adjusted odds ratio [aOR], 0.75; 95% confidence interval [CI], 0.49-1.15). In secondary analyses, intended cesarean delivery was not associated with blood transfusion (aOR, 0.71; 95% CI, 0.34-1.50) or readmission within 90 days (aOR, 0.60; 95% CI, 0.32-1.14). In the sensitivity analysis, cesarean delivery was associated with a 3-fold higher risk of nontransfusion morbidity compared to vaginal delivery (aOR, 2.64; 95% CI, 1.54-3.93), a 3-fold higher risk of blood transfusion (aOR, 3.06; 95% CI, 1.17-7.99), and a 2-fold higher risk of readmission within 90 days (aOR, 2.20; 95% CI, 1.09-4.46) compared to vaginal delivery. Among pregnant patients with pulmonary hypertension, a trial of labor was not associated with a higher risk of morbidity compared to an intended cesarean delivery. One-third of patients who required an intrapartum cesarean delivery had a morbidity event, demonstrating the increased risk of adverse events in this group.

Comparative Effectiveness of Natalizumab, Fingolimod, and Injectable Therapies in Pediatric-Onset Multiple Sclerosis: A Registry-Based Study.

Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses, and though patients with POMS usually recover from relapses better than adults, patients with POMS reach irreversible disability at a younger age than adult-onset patients. There have been few randomized, placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry. This retrospective study included patients with POMS who initiated treatment with an injectable DMT, natalizumab, or fingolimod between January 1, 2006, and May 3, 2021. Patients were matched using inverse probability treatment weighting. The primary outcome was time to first relapse from index therapy initiation. Secondary study outcomes included annualized relapse rate; proportions of relapse-free patients at 1, 2, and 5 years; time to treatment discontinuation; and times to 24-week confirmed disability worsening and confirmed disability improvement. A total of 1,218 patients with POMS were included in this analysis. Patients treated with fingolimod had a significantly lower risk of relapse than patients treated with injectable DMTs (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29-0.83; p = 0.008). After adjustment for prior DMT experience in the unmatched sample, patients treated with natalizumab had a significantly lower risk of relapse than patients treated either with injectable DMTs (HR, 0.15; 95% CI 0.07-0.31; p < 0.001) or fingolimod (HR, 0.37; 95% CI 0.14-1.00; p = 0.049). The adjusted secondary study outcomes were generally consistent with the primary outcome or with previous observations. The findings in the inverse probability treatment weighting-adjusted patient populations were confirmed in multiple sensitivity analyses. Our analyses of relapse risk suggest that natalizumab is more effective than fingolimod in the control of relapses in this population with high rates of new inflammatory activity, consistent with previous studies of natalizumab and fingolimod in adult-onset patients and POMS. In addition, both fingolimod and natalizumab were more effective than first-line injectable therapies. This study provides Class II evidence that patients with POMS treated with natalizumab had a lower risk of relapse than those with fingolimod.

Remote Ischemic Conditioning With Medical Management or Reperfusion Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Remote ischemic conditioning (RIC) is a low-cost, accessible, and noninvasive neuroprotective treatment strategy, but its efficacy and safety in acute ischemic stroke are controversial. With the publication of several randomized controlled trials (RCTs) and the recent results of the RESIST trial, it may be possible to identify the patient population that may (or may not) benefit from RIC. This systematic review and meta-analysis aims to evaluate the effectiveness and safety of RIC in patients with ischemic stroke receiving different treatments by pooling data of all randomized controlled studies to date. We searched the PubMed, Embase, Cochrane, Elsevier, and Web of Science databases to obtain articles in all languages from inception until May 25, 2023. The primary outcome was the modified Rankin Scale (mRS) score at the specified endpoint time in the trial. The secondary outcomes were change in NIH Stroke Scale (NIHSS) and recurrence of stroke events. The safety outcomes were cardiovascular events, cerebral hemorrhage, and mortality. The quality of articles was evaluated through the Cochrane risk assessment tool. This study was registered in PROSPERO (CRD42023430073). There were 7,657 patients from 22 RCTs included. Compared with the control group, patients who received RIC did not have improved mRS functional outcomes, regardless of whether they received medical management, reperfusion therapy with intravenous thrombolysis (IVT), or mechanical thrombectomy (MT). In the medical management group, patients who received RIC had decreased incidence of stroke recurrence (risk ratio 0.63, 95% CI 0.43-0.92, p = 0.02) and lower follow-up NIHSS score by 1.72 points compared with the control group (p < 0.00001). There was no increased risk of adverse events including death or cerebral hemorrhage in the IVT or medical management group. In patients with ischemic stroke who are not eligible for reperfusion therapy, RIC did not affect mRS functional outcomes but significantly improved the NIHSS score at the follow-up endpoint and reduced stroke recurrence, without increasing the risk of cerebral hemorrhage or death. In patients who received IVT or MT, the benefit of RIC was not observed.

Impact of HIV Infection on Liver and Cardiovascular Outcomes in Veterans With Metabolic Dysfunction-Associated Steatotic Liver Disease.

Hepatic steatosis is highly prevalent in people living with HIV. It remains unclear whether HIV in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with greater risks of liver disease progression and cardiovascular disease (CVD). We aim to evaluate the impact of HIV infection on risks of liver and CVD outcomes among US Veterans with MASLD. Using national Veterans Administration data from 2010 to 2022, we created a propensity score-matched cohort of MASLD patients with vs without HIV. Primary outcomes were incidence of cirrhosis and hepatocellular carcinoma (HCC) among patients with vs without HIV and patients with MASLD-HIV on antiretroviral therapy (ART) vs not on ART. Secondary outcomes included incidence of major adverse cardiovascular events and overall survival. The propensity-matched cohort included 920 MASLD patients with HIV and 920 MASLD patients without HIV and was similar in demographics and comorbidities. Compared with MASLD patients without HIV, incidences of cirrhosis and HCC were similar among MASLD with HIV. Compared with MASLD patients without HIV, incidence of major adverse cardiovascular event was higher among MASLD patients with HIV (5.18 vs 4.48 per 100 person-years, P = 0.03). Overall 5-year survival was significantly lower among MASLD patients with HIV and even lower among those not on ART. Among US Veterans with MASLD, concurrent HIV infection, and particularly not being on ART, is associated with greater risks of CVD and decreased overall survival. No differences in risks of cirrhosis or HCC were observed.

Prevalence and predictive factors of colorectal sessile serrated lesions in younger individuals.

Sessile serrated lesions (SSLs) are obscured lesions predominantly in the right-sided colon and associated with interval colorectal cancer; however, their prevalence and risk factors among younger individuals remain unclear. This retrospective study enrolled individuals who underwent index colonoscopy. The primary outcome was the SSL prevalence in the younger (<50 years) and older (≥50 years) age groups, while the secondary outcomes included clinically significant serrated polyps (CSSPs). Multivariable logistic regression was employed to identify predictors. Of the 9854 eligible individuals, 4712 (47.8%) were categorized into the younger age group. Individuals in the younger age group exhibited lower prevalences of adenomas (22.6% vs. 46.2%; P<0.001) and right-sided adenomas (11.2% vs. 27.2%; P<0.001) compared with their older counterparts. However, both groups exhibited a similar prevalence of SSLs (7.2% vs. 6.5%; P=0.16) and CSSPs (10.3% vs. 10.3%;P=0.96). Multivariable analysis revealed that age 40-49 years (odds ratio [OR] 1.81, 95%CI 1.01-3.23), longer withdrawal time (OR 1.17, 95%CI 1.14-1.20, per minute increment), and endoscopist performance (OR 3.35, 95%CI 2.44-4.58) were independent predictors of SSL detection in the younger age group. No significant correlation was observed between adenoma and SSL detection rates among endoscopists. SSLs are not uncommon among younger individuals. Moreover, diligent effort and expertise are of paramount importance in SSL detection. Future studies should explore the clinical significance of SSLs in individuals of younger age.

The Effect of an Oxytocin Decision Support Checklist on Oxytocin Use and Maternal and Neonatal Outcomes: A Retrospective Cohort Study.

To assess the association between use of an oxytocin decision support checklist with oxytocin usage and clinical outcomes. We conducted a retrospective cohort study of patients with singleton gestations at 370/7 weeks or greater who received oxytocin during labor from October 2012 to February 2017 at an integrated community health care system during three exposure periods: (1) pre-checklist; (2) after paper checklist implementation; and (3) after checklist integration into the electronic medical record (EMR). The checklist was a clinical decision support tool to standardize the dosing and management of oxytocin. Thus, our primary outcomes included oxytocin infusion rates and cumulative dose. Secondary outcomes included maternal and neonatal outcomes. We controlled for maternal risk factors with multivariable regression analysis and stratified by mode of delivery. A total of 34,269 deliveries were included. Unadjusted analyses showed that compared with pre-checklist, deliveries during the paper and EMR-integrated periods had a lower cumulative dose (4,670 ± 6,174 vs. 4,318 ± 5,719 and 4,286 ± 5,579 mU, p < 0.001 for both), lower maximal infusion rate (9.9 ± 6.8 vs. 8.7 ± 5.8 and 8.4 ± 5.6 mU/min, p < 0.001 for both), and longer duration of oxytocin use (576 ± 442 vs. 609 ± 476 and 627 ± 488 minutes, p < 0.001 and p = 0.01, respectively). The unadjusted rates of cesarean, 5-minute Apgar <7, mechanical ventilation, and neonatal hospital length of stay were similar between periods. The adjusted mean difference in time from admission to delivery was longer during the EMR-integrated period compared with pre-checklist (3.0 [95% confidence interval: 2.7-3.3] hours, p < 0.001). Oxytocin checklist use was associated with decreased oxytocin use patterns at the expense of longer labor times. Findings were more pronounced with EMR integration. · An oxytocin decision support checklist is associated with reduced amounts of oxytocin used.. · However, checklists were associated with longer duration of oxytocin use and of labor.. · Results were more pronounced in the EMR-integrated checklist compared with paper checklist..