Relative Rate Reduction Research Articles

VPExam in Heart Failure Innovating Virtual Cardiac Care

Telehealth and Virtual care are growing fields of importance, but the loss of comprehensive physical exam creates barriers to managing complex patients especially those with heart failure. Disruptive digital tools such as VPExam virtual care combine augmented reality instruction of visuals with bluetooth stethoscopes and ECGs to improve accuracy by assessing volume status, cardiopulmonary auscultation, arrythmia detection, and providing structured data including remote patient monitoring (RPM) data, vitals, medication reconciliation, and labs. VPExam intervention has significantly improved outcomes for high-risk and underserved populations with heart failure discharged to Skilled Nursing Facilities and Home Care. VPExam QI revealed workflows for both routine and urgent cardiology consultation following heart failure hospitalizations resulted in moderate significance modification in clinical management in 84% of encounters, while being associated with a 40% relative risk reduction in 30-day hospital readmission rate and a 56% relative risk reduction in 30-day mortality rate. The review summarizes both challenges to cardiac transitions of care and the evolution of cardiac virtual care with actionable physical exam data to optimize readmissions and mortality that is especially relevant to the underserved populations of skilled nursing facilities and home bound patients served by home care agencies.

Investigation of Lithium-Ion Battery Performance Utilizing Magnetic Controllable Superionic Conductor Li3(V1-x Fe x )2(PO4)3/C (x = 0.05 and 0.10).

Lithium-ion batteries with Li3V2(PO4)3/C as the cathode have been a popular research topic in recent years; however, studies of the effects of external magnetic fields on them are less common. This study investigates the effects of an external magnetic field applied parallel to the direction of the anode and cathode on the ion transport through iron-doped Li3(V1-x Fe x )2(PO4)3, the outer carbon coating, the film/electrolyte/separator, and up to the lithium metal electrode on a microscopic level. The results reveal that for the x = 0.05 sample with lower doping, the magnetostriction expansion of Li3(V1-x Fe x )2(PO4)3 and the magnetostrictive contraction effect of the outer ordered carbon layer cancel each other out, resulting in no significant enhancement of the battery's energy and power density due to the external magnetic field. In contrast, the x = 0.1 sample, lacking magnetostrictive contraction in the outer ordered carbon layer, shows that its energy and power density can be influenced by the magnetic field. Under zero magnetic field, the cyclic performance exhibits superior average capacity performance in the x = 0.05 sample, while the x = 0.1 sample shows a lower decay rate. Both samples are affected by the magnetic field; however, the x = 0.1 sample performs better under magnetic conditions. In particular, in the C-rate tests under a magnetic field, the sample with x = 0.1 showed a significant relative reduction in capacity decay rate by 20.18% compared to the sample with x = 0.05.

Heavy metal tolerance and accumulation in the Brassica species (Brassica chinensis var. parachinensis and Brassica rapa L.): A pot experiment

This study delves into the heavy metal tolerance and accumulation capabilities of Brassica chinensis var. parachinensis (B. chinensis) and Brassica rapa L. (B. rapa) in a pot experiment, specifically focusing on cadmium (Cd), chromium (Cr) and lead (Pb). Agricultural topsoils were spiked with varying concentrations of these heavy metals (0 mg/kg, 75 mg/kg, 150 mg/kg, 225 mg/kg and 300 mg/kg) for each element. The experiment involved cultivating 15 pots each of B. chinensis and B. rapa over 60 days. Results indicated that both Brassica species experienced delayed germination, with B. chinensis exhibiting a significant drop in germination percentage to 53 % at the highest concentration (300 mg/kg), while B. rapa showed a tendency for an increased germination percentage of up to 80 % at elevated metal concentrations; however, these differences were not statistically significant. Both B. chinensis and B. rapa demonstrated a stable decline in growth rate from 0.05 cm/day to 0.04 cm/day with increasing heavy metal concentrations, and the he reduction in relative growth rate was significant at the highest concentration compared to the control. The stress tolerance index revealed a significant decrease in plant heights for B. chinensis, in contrast to the stable performance of B. rapa, showcasing the tolerance of B. rapa to toxic conditions. Despite insignificant differences in fresh biomass due to metal treatments, B. chinensis consistently yielded higher biomass, yet it had a lower edible index due to its higher root biomass. Leaf areas increased significantly in both species at higher soil treatments, while root lengths remained unchanged, suggesting their resilience to elevated heavy metal concentrations. Analysis of plant tissues (leaves, stems and roots) using ICP-OES revealed that B. rapa accumulated the highest Cd concentration (864 mg/kg), whereas B. chinensis accumulated the highest Pb concentration (953 mg/kg) in root parts. Both species significantly accumulated Cr in roots, demonstrating a sequestration mechanism. These findings suggest that both species, particularly, B. rapa possess strong tolerance and accumulation capabilities for non-essential heavy metals, making them potential hyperaccumulators for green remediation techniques in toxic soil environments. Understanding the molecular mechanisms driving these responses and validating phytoremediation potential in real-world scenarios is essential for developing sustainable soil management practices.

Visual Hallucination Elevates Speech Recognition

Due to the detrimental impact of noise on the conventional audio speech recognition (ASR) task, audio-visual speech recognition~(AVSR) has been proposed by incorporating both audio and visual video signals. Although existing methods have demonstrated that the aligned visual input of lip movements can enhance the robustness of AVSR systems against noise, the paired videos are not always available during inference, leading to the problem of the missing visual modality, which restricts their practicality in real-world scenarios. To tackle this problem, we propose a Discrete Feature based Visual Generative Model (DFVGM) which exploits semantic correspondences between the audio and visual modalities during training, generating visual hallucinations in lieu of real videos during inference. To achieve that, the primary challenge is to generate the visual hallucination given the noisy audio while preserving semantic correspondences with the clean speech. To tackle this challenge, we start with training the audio encoder in the Audio-Only (AO) setting, which generates continuous semantic features closely associated with the linguistic information. Simultaneously, the visual encoder is trained in the Visual-Only (VO) setting, producing visual features that are phonetically related. Next, we employ K-means to discretize the continuous audio and visual feature spaces. The discretization step allows DFVGM to capture high-level semantic structures that are more resilient to noise and generate visual hallucinations with high quality. To evaluate the effectiveness and robustness of our approach, we conduct extensive experiments on two publicly available datasets. The results demonstrate that our method achieves a remarkable 53% relative reduction (30.5%->12.9%) in Word Error Rate (WER) on average compared to the current state-of-the-art Audio-Only (AO) baselines while maintaining comparable results (< 5% difference) under the Audio-Visual (AV) setting even without video as input.

Benefits of intravenous iron supplementation in heart failure.

Introduction: Iron deficiency (ID) is one of the most frequent comorbidities in patients with heart failure (HF) and is estimated to be present in up to 80% of acute patients regardless of their ejection fraction. Randomized controlled trials have shown that supplementary intravenous iron results in improved clinical outcomes; however, the current understanding of the effects of intravenous iron on morbidity and mortality remains limited. Study and results: The meta-analysis pooled individual participant data from three randomized placebo-controlled trials of ferric carboxymaltose (FCM) in adult patients (n = 4,501) with heart failure and iron deficiency (CONFIRM-HF, AFFIRM-AHF, and HEART-FID). FCM therapy significantly reduced the co-primary composite endpoint of total cardiovascular hospitalizations and cardiovascular death, with a rate ratio (RR 0.86; 95% CI 0.75 to 0.98; p = 0.029). FCM therapy was associated with a 17% relative rate reduction in total cardiovascular hospitalizations (RR 0.83; 95% CI 0.73 to 0.96; p = 0.009) and a 16% relative rate reduction in total heart failure hospitalizations (RR 0.84; 95% CI 0.71 to 0.98; p = 0.025). Lessons learned: The meta-analysis shows that in iron-deficient patients with heart failure and reduced or mildly reduced left ventricular ejection fraction, intravenous ferric carboxymaltose (FCM) is associated with a reduced risk of total cardiovascular hospitalization and cardiovascular mortality. These findings indicate that intravenous FCM should be considered in iron-deficient patients with heart failure and reduced or mildly reduced ejection fractions.

Comparing Lung Cancer Screening Strategies in a Nationally Representative US Population Using Transportability Methods for the National Lung Cancer Screening Trial

The National Lung Screening Trial (NLST) found that screening for lung cancer with low-dose computed tomography (CT) reduced lung cancer-specific and all-cause mortality compared with chest radiography. It is uncertain whether these results apply to a nationally representative target population. To extend inferences about the effects of lung cancer screening strategies from the NLST to a nationally representative target population of NLST-eligible US adults. This comparative effectiveness study included NLST data from US adults at 33 participating centers enrolled between August 2002 and April 2004 with follow-up through 2009 along with National Health Interview Survey (NHIS) cross-sectional household interview survey data from 2010. Eligible participants were adults aged 55 to 74 years, and were current or former smokers with at least 30 pack-years of smoking (former smokers were required to have quit within the last 15 years). Transportability analyses combined baseline covariate, treatment, and outcome data from the NLST with covariate data from the NHIS and reweighted the trial data to the target population. Data were analyzed from March 2020 to May 2023. Low-dose CT or chest radiography screening with a screening assessment at baseline, then yearly for 2 more years. For the outcomes of lung-cancer specific and all-cause death, mortality rates, rate differences, and ratios were calculated at a median (25th percentile and 75th percentile) follow-up of 5.5 (5.2-5.9) years for lung cancer-specific mortality and 6.5 (6.1-6.9) years for all-cause mortality. The transportability analysis included 51 274 NLST participants and 685 NHIS participants representing the target population (of approximately 5 700 000 individuals after survey-weighting). Compared with the target population, NLST participants were younger (median [25th percentile and 75th percentile] age, 60 [57 to 65] years vs 63 [58 to 67] years), had fewer comorbidities (eg, heart disease, 6551 of 51 274 [12.8%] vs 1 025 951 of 5 739 532 [17.9%]), and were more educated (bachelor's degree or higher, 16 349 of 51 274 [31.9%] vs 859 812 of 5 739 532 [15.0%]). In the target population, for lung cancer-specific mortality, the estimated relative rate reduction was 18% (95% CI, 1% to 33%) and the estimated absolute rate reduction with low-dose CT vs chest radiography was 71 deaths per 100 000 person-years (95% CI, 4 to 138 deaths per 100 000 person-years); for all-cause mortality the estimated relative rate reduction was 6% (95% CI, -2% to 12%). In the NLST, for lung cancer-specific mortality, the estimated relative rate reduction was 21% (95% CI, 9% to 32%) and the estimated absolute rate reduction was 67 deaths per 100 000 person-years (95% CI, 27 to 106 deaths per 100 000 person-years); for all-cause mortality, the estimated relative rate reduction was 7% (95% CI, 0% to 12%). Estimates of the comparative effectiveness of low-dose CT screening compared with chest radiography in a nationally representative target population were similar to those from unweighted NLST analyses, particularly on the relative scale. Increased uncertainty around effect estimates for the target population reflects large differences in the observed characteristics of trial participants and the target population.

The effect of insulin analogs in people with type 1 diabetes at increased risk of severe hypoglycemia

Type 1 diabetes is characterized by insulin deficiency, and treatment is to supply insulin mimicking the physiological endogenous insulin secretion. Since its discovery, insulin therapy has evolved, and since the 1990s, an increasing number of insulin analogs with various pharmacokinetic and pharmacodynamic profiles have become available. Despite the improvement of insulin therapy, hypoglycemia remains the main side effect and is a daily concern for many people with diabetes and their families. A proportion of people with type 1 diabetes are at increased risk of hypoglycemia and experience recurring episodes. When designing insulin trials, this group of people is most often excluded in order to reduce the risk of adverse study outcomes, even though it may be the group that may benefit the most from treatment with new insulins. The results of the phase III trials, therefore, underestimate the clinical impact and pharmacoeconomic effect of the implementation of new insulins in the broader type 1 diabetes population. This paper reviews the four insulin trials that include people at increased risk of hypoglycemia. In general, the studies confirm the results from phase III trials in terms of similar reduction and maintenance of HbA1c, as well as relative rate reductions of hypoglycemia. However, the absolute treatment differences in the reduction of hypoglycemia are even greater in the trials, including people at high risk of hypoglycemia. This emphasizes the importance of including people at high risk of hypoglycemia to assess the full clinical and pharmacoeconomic benefit of new insulins.

Response strategies of stem/leaves endophyte communities to nano-plastics regulate growth performance of submerged macrophytes

Research on the toxicity effects of nano-plastics on submerged macrophytes has been increasing over the past several years. However, how the endophytic bacteria of submerged macrophytes respond to nano-plastics remains unknown, although they have been widely shown to help terrestrial plants cope with various environmental stressors. Here, a microcosm experiment was performed to unravel the effects of high concentration of nano-plastics (20 mg/L) on three submerged macrophyte (Vallisneria natans, Potamogeton maackianus, Myriophyllum spicatum) and their endophytic bacterial communities. Results indicated that nano-plastics induced antioxidative stress in plants, but significantly reduction in relative growth rate (RGR) only occurred in V. natans (from 0.0034 to −0.0029 day-1), accompanied by change in the stem/leaves endophyte community composition. Further analysis suggested nano-plastics caused a reduction in environmental nutrient availability and the proportion of positive interactions between endophyte communities (43%), resulting in the lowest RGR of V. natans. In contrast, endophytes may help P. maackianus and M. spicatum cope with nano-plastic stress by increasing the proportion of positive correlations among communities (70% and 75%), leaving their RGR unaffected. Collectively, our study elucidates the species-specific response strategies of submerged macrophyte-endophyte to nano-plastics, which helps to reveal the different phytoremediation potential of submerged macrophytes against nano-plastic pollution.

Comparison of Transcatheter Arterialization of Deep Veins to Standard of Care in Patients with No-Option Chronic Limb Threatening Ischemia

Patients with no-option chronic limb-threatening ischemia (no-option CLTI) have limited therapeutic options. The PROMISE II study evaluated, transcatheter arterialization of deep veins (TADV) as a treatment option for no-option CLTI. In the current study patients from PROMISE II were compared to patients from a registry of untreated no-option CLTI patients (CLariTI: Natural Progression of High-Risk Chronic Limb-Threatening Ischemia). We used propensity matching to compare patients from the PROMISE II prospective study of the TADV intervention with simultaneously enrolled CLTI patients that were note candidates for PROMISE II but were enrolled in to CLariTI natural history registry. Untreated no-option CLTI (CLariTI) patients could either be no-option or patients who did not meet PROMISE II entry criteria. Risk difference between groups was calculated using common risk difference and P values were provided by propensity-score stratified Mantel-Haenszel test. The primary endpoint was amputation-free survival (AFS). Diabetes was present in over 75% of patients. All patients had tissue loss and 35-46% had extensive tissue loss (Rutherford 6). The unadjusted AFS at 6months, was 66.1% by Kaplan-Meier estimate for PROMISE II patients (n=105) compared to 39.1% in the no-option cohort of CLariTI (n=121) and 44.0% in the full cohort (no-option and patients not meeting entry criteria combine, n=180). The treatment group who underwent TADV for no-option CLTI had an absolute difference of 29% improved (P<0.0001) propensity-adjusted risk difference in AFS and a relative event rate reduction of 45% compared to the no-option control patients. Transcatheter arterialization of deep veins (TADV) resulted in improved 6month AFS in no-option CLTI patients and appears to be a promising therapy in patients with no-option CLTI.

An observer-blinded, cluster randomised trial of a typhoid conjugate vaccine in an urban South Indian cohort

BackgroundTyphoid fever causes nearly 110,000 deaths among 9.24 million cases globally and disproportionately affects developing countries. As a control measure in such regions, typhoid conjugate vaccines (TCVs) are recommended by the World Health Organization (WHO). We present here the protocol of a cluster randomised vaccine trial to assess the impact of introducing TyphiBEV® vaccine to those between 1 and 30 years of age in a high-burden setting.MethodsThe primary objective is to determine the relative and absolute rate reduction of symptomatic, blood-culture-confirmed S. Typhi infection among participants vaccinated with TyphiBEV® in vaccine clusters compared with the unvaccinated participants in non-vaccine clusters. The study population is residents of 30 wards of Vellore (a South Indian city) with participants between the ages of 1 and 30 years who provide informed consent. The wards will be divided into 60 contiguous clusters and 30 will be randomly selected for its participants to receive TyphiBEV® at the start of the study. No placebo/control is planned for the non-intervention clusters, which will receive the vaccine at the end of the trial. Participants will not be blinded to their intervention. Episodes of typhoid fever among participants will be captured via stimulated, passive fever surveillance in the area for 2 years after vaccination, which will include the most utilised healthcare facilities. Observers blinded to the participants’ intervention statuses will record illness details. Relative and absolute rate reductions will be calculated at the end of this surveillance and used to estimate vaccine effectiveness.DiscussionThe results from our trial will allow countries to make better-informed decisions regarding the TCV that they will roll-out and may improve the global supplies and affordability of the vaccines.Trial registrationClinical Trials Registry of India (CTRI) CTRI/2022/03/041314. Prospectively registered on 23 March 2022 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62548&EncHid=&userName=vellore%20typhoid). CTRI collects the full WHO Trial Registration Data Set.

Bioprotective potential of maize apoplastic fluid bacterium (Bacillus amyloliquefaciens) and arbuscular mycorrhizal fungi (Glomus intraradices) against Spodoptera frugiperda infestation in maize

Spodoptera frugiperda is an invasive polyphagous pest of cereal crops and responsible for less maize production in the past. Development of bioprotective agents to reduce the impact of this biotic stress is essential. The present investigation was done to evaluate whether co-inoculation of maize with two endophytes such as Bacillus amyloliquefaciens and Glomus intraradices could alter the level of antioxidants and defense enzymes in maize and affect the feeding behavior of S. frugiperda on maize. The results indicated higher activity of antioxidants (catalases - 106.26%, peroxidases - 62.71%, superoxide dismutase −17.39% and ascorbate oxidase - 160.00%) and defensive enzymes (polyphenol oxidases - 205.86%, phenylalanine ammonia lyases - 126.00% and lipoxygenases - 33.33%) in leaves of B.amyloliquefaciens and G.intraradices treated maize after fed with S. frugiperda (96 h) over control. The total phenolics and dry biomass content were also higher in B. amyloliquefaciens and G. intraradices inoculated plants after S. frugiperda infestation (96 h). Leaf feeding bioassay indicated reduction in relative consumptive rate (18.25%), relative growth rate (19.76%) and increased feeding deterrence index (15.50%) of S. frugiperda when fed on B. amyloliquefaciens and G. intraradices inoculated maize for 24 h Inoculation of maize with B. amyloliquefaciens and G. intraradices significantly altered the defense parameters of maize which are directly linked with reduced feeding and growth rate of S. frugiperda. Therefore, these endophytes can be used to reduce the usage of chemical insecticides or be a part in integrated pest management systems for sustainable agriculture production.

Longitudinal Clinical and MRI Outcomes in Relapsing Multiple Sclerosis (RMS) Patients After Short-term Ponesimod Treatment Interruption and Re-initiation (P6-3.007)

Longitudinal Clinical and MRI Outcomes in Relapsing Multiple Sclerosis (RMS) Patients After Short-term Ponesimod Treatment Interruption and Re-initiation (P6-3.007)

Evaluating the impact of radiofrequency spectroscopy on reducing reoperations after breast conserving surgery: A meta-analysis.

The benefits of breast conserving surgery for breast cancer patients are well established. To achieve adequate margins of excision, intraoperative management of breast margins is a critical factor through reducing reoperation for inadequate positive margin excision and associated morbidity and cost. Radiofrequency spectroscopy is a technology that could significantly reduce positive margins when used intraoperatively as an adjunct to other margin management methods. A meta-analysis was completed with 10 publications comparing use of radiofrequency spectroscopy technology (MarginProbe) with standard margin assessment procedures. Three randomized controlled studies and seven retrospective studies comparing MarginProbe to historical controls were included. The primary endpoint was reduction of re-excision rates. Statistical significance level was set at the two-sided 5% level corresponding to two-sided 95% confidence intervals (CIs) of the pooled relative risk estimates. A total of 2335 patients from 10 publications were included in this meta-analysis. The overall relative reduction in re-excision rate was 0.49 (95% CI: 0.38-0.64, p < 0.001). Statistical methods were used to examine publication bias. Despite the limited randomized controlled trials available comparing radiofrequency spectroscopy to standard operation procedures, the data from the 10 studies demonstrate a statistically significant reduction in re-excision rate of 49% for MarginProbe usage, currently the only technology indicated for intraoperative identification of breast cancer tissue at the lumpectomy specimen margin.

Lower Double-Wall Puncture Rate During Ultrasound-Guided Internal Jugular Vein Cannulation Using Sharper, Narrower-Gauge, and/or Length-Optimized Needles: A 6-Year Quality Improvement Clinical Series in Adult Patients.

Background: During internal jugular vein (IJV) cannulation, needle tip injury to vulnerable subjacent cervical anatomic structures can be prevented if the cannulating needle tip is not permitted, even momentarily, to penetrate the deep portion of the IJV wall, an event known as double-wall puncture (DWP), also called posterior wall puncture. Methods: We conducted a 6-year ultrasound-guided IJV cannulation quality improvement project, seeking to minimize the occurrence of DWP in 228 adult patients using needles of different gauge and tip sharpness. Most needles were length-optimized to the distance between the skin puncture site and the IJV mid-lumen for a selected angle of needle insertion by (1) using a nylon screw-on needle stop or (2) using a cannulating needle that already had the desired shaft length. Results: Standard central venous cannulation kit needles were long enough to reach or traverse the deepest portion of the IJV wall in nearly all patients. Use of extra-sharp, smaller-diameter needles in place of standard needles was associated with a 26.3% relative reduction in DWP rate. Use of needles length-optimized to reach only the IJV mid-lumen was associated with a 78.4% relative reduction in DWP rate. A 0% DWP rate was attained using length-optimized 21-gauge extra-sharp needles and length-optimized 20-gauge needles of intermediate sharpness. Conclusion: The 9.2% DWP rate achieved during this project was approximately half the rate reported at the time of project inception. Use of length-optimized, sharper, narrower-gauge cannulating needles may help avoid DWP during ultrasound-guided IJV cannulation.

Assessing the impact of a national clinical guideline for the management of chronic pain on opioid prescribing rates: a controlled interrupted time series analysis

BackgroundOpioids can be effective analgesics, but long-term use may be associated with harms. In 2013, the first national, comprehensive, evidence-based pain management guideline was published, from the Scottish Intercollegiate Guideline Network (SIGN 136: Management of Chronic Pain) with key recommendations on analgesic prescribing. This study aimed to examine the potential impact on national opioid prescribing rates in Scotland.MethodsTrends in national and regional community opioid prescribing data for Scotland were analysed from quarter one (Q1) 2005 to Q2 2020. Interrupted time series regression examined the association of SIGN 136 publication with prescribing rates for opioid-containing drugs. Gabapentinoid prescribing was used as a comparison drug.ResultsAfter a positive prescribing trend pre-publication, the timing of SIGN 136 publication was associated with a negative change in the trend of opioid prescribing rates (−2.82 items per 1000 population per quarter [PTPPQ]; P < 0.01). By Q2 2020, the relative reduction in the opioid prescribing rate was −20.67% (95% CI: −23.61, −17.76). This persisted after correcting for gabapentinoid prescribing and was mainly driven by the reduction in weak opioids, whereas strong opioid prescribing rates continued to rise. Gabapentinoid prescribing showed a significant rise in level (8.00 items per 1000 population; P = 0.01) and trend (0.27 items PTPPQ; P = 0.01) following SIGN 136 publication.ConclusionsThe publication of SIGN 136 was associated with a reduction in opioid prescribing rates. This suggests that changes in clinical policy through evidence-based national clinical guidelines may affect community opioid prescribing, though this may be partially replaced by gabapentinoids, and other factors may also contribute.

Eslicarbazepine Acetate as Adjunctive Therapy for Primary Generalized Tonic-Clonic Seizures in Adults: A Prospective Observational Study.

BackgroundEslicarbazepine acetate (ESL), a novel sodium channel blocker, is approved for mono and adjunctive treatment of partial epileptic seizures with or without secondary generalization. Its efficacy in primary generalized seizures has not yet been evaluated.ObjectiveTo evaluate the efficacy and safety of ESL in primary generalized tonic-clonic seizures (PGTCS) in an observational study.MethodsThe data were collected from a prospective population-based register. Effectiveness was measured as relative reduction in standardized seizure frequency (SSF), responder rate (≥ 50% reduction in SSF), and seizure freedom rate at 6 and 12 months after initiation of ESL. Safety and tolerability were evaluated using patients’ diaries.ResultsFifty-six adult patients with PGTCS were treated with ESL as adjunctive therapy. Of these, 30.4% (n = 17) had myoclonic seizures in addition to PGTCS. The retention rate after 12 months was 80.4% (n = 45). After initiating ESL therapy, reduction in SSF for PGTCS on ESL was 56.0% after 6 months and 56.9% after 12 months (p < 0.01), whereas myoclonic seizures did not show any significant improvement in frequency. The responder rate for PGTCS was 64.3% after 6 months and 66.1% after 12 months, and seizure freedom was achieved in 32.1% and 35.7%, respectively. Forty-three patients (73.2%) reported no side effects. Among the reported side effects of ESL therapy, headache (7.1%), dizziness (8.9%), tiredness (7.1%), nausea (5.4%), and hyponatremia (5.4%) were the most prevalent.ConclusionsOur data suggest that ESL may provide additional benefits in the treatment of patients with PGTCS and motivate randomized controlled trials in this indication.

A prospective, randomized assessment of a novel, local antibiotic releasing platform for the prevention of superficial and deep surgical site infections

BackgroundDespite significant advances in infection control guidelines and practices, surgical site infections (SSIs) remain a substantial cause of morbidity, prolonged hospitalization, and mortality among patients having both elective and emergent surgeries. D-PLEX100 is a novel, antibiotic-eluting polymer–lipid matrix that supplies a high, local concentration of doxycycline for the prevention of superficial and deep SSIs. The aim of our study was to evaluate the safety and efficacy of D-PLEX in addition to standard of care (SOC) in preventing superficial and deep surgical site infections for patients undergoing elective colorectal surgery.MethodsFrom October 10, 2018 to October 6, 2019, as part of a Phase 2 clinical trial, we randomly assigned 202 patients who had scheduled elective colorectal surgery to receive either standard of care SSI prophylaxis or D-PLEX100 in addition to standard of care. The primary objective was to assess the efficacy of D-PLEX100 in superficial and deep SSI reduction, as measured by the incidence of SSIs within 30 days, as adjudicated by both an individual assessor and a three-person endpoint adjudication committee, all of whom were blinded to study-group assignments. Safety was assessed by the stratification and incidence of treatment-emergent adverse events.ResultsOne hundred and seventy-nine patients were evaluated in the per protocol population, 88 in the intervention arm [51 males, 37 females, median age (64.0 range: 19–92) years] and 91 in the control arm [57 males, 34 females, median age 64.5 (range: 21–88) years]. The SSI rate within 30 day post-index surgery revealed a 64% relative risk reduction in SSI rate in the D-PLEX100 plus standard of care (SOC) group [n = 7/88 (8%)] vs SOC alone [n = 20/91 (22%)]; p = 0.0115. There was no significant difference in treatment-emergent adverse events.ConclusionsD-PLEX100 application leads to a statistically significant reduction in superficial and deep surgical site infections in this colorectal clinical model without any associated increase in adverse events.

Preventing Cardiac Arrest in the Pediatric Cardiac Intensive Care Unit Through Multicenter Collaboration

Preventing in-hospital cardiac arrest (IHCA) likely represents an effective strategy to improve outcomes for critically ill patients, but feasibility of IHCA prevention remains unclear. To determine whether a low-technology cardiac arrest prevention (CAP) practice bundle decreases IHCA rate. Pediatric cardiac intensive care unit (CICU) teams from the Pediatric Cardiac Critical Care Consortium (PC4) formed a collaborative learning network to implement the CAP bundle consistent with the Institute for Healthcare Improvement framework; 15 hospitals implemented the bundle voluntarily. Risk-adjusted IHCA incidence rates were analyzed across 2 time periods, 12 months (baseline) and 18 months after CAP implementation (intervention) using difference-in-differences (DID) regression to compare 15 CAP and 16 control PC4 hospitals that chose not to participate in CAP but had IHCA rates tracked in the PC4 registry. Patients deemed at high risk for IHCA, based on a priori evidence-based criteria and empirical hospital-specific criteria, were selected to receive the CAP bundle. Data were collected from July 2018 to December 2019, and data were analyzed from March to August 2020. CAP bundle included 5 elements developed to promote increased situational awareness and communication among bedside clinicians to recognize and mitigate deterioration in high-risk patients. Risk-adjusted IHCA incidence rate across all CICU admissions (IHCA events divided by all admissions). The bundle was activated in 2664 of 10 510 CAP hospital admissions (25.3%); admission characteristics were similar across study periods. There was a 30% relative reduction in risk-adjusted IHCA incidence rate at CAP hospitals (intervention period: 2.6%; 95% CI, 2.2-2.9; baseline: 3.7%; 95% CI, 3.1-4.0), but no change at control hospitals (intervention period: 2.7%; 95% CI, 2.3-2.9; baseline: 2.7%; 95% CI, 2.2-3.0). DID analysis confirmed significantly reduced odds of IHCA among all admissions at CAP hospitals compared with control hospitals during the intervention period vs baseline (odds ratio, 0.72; 95% CI, 0.56-0.91; P = .01). DID odds ratios were 0.72 (95% CI, 0.53-0.98) for the surgical subgroup, 0.74 (95% CI, 0.48-1.14) for the medical subgroup, and 0.72 (95% CI, 0.50-1.03) for the high-risk admission subgroup at CAP hospitals after intervention. All-cause risk-adjusted mortality rate did not change after intervention. Implementation of this CAP bundle led to significant IHCA reduction across multiple pediatric CICUs. Future studies may determine if this bundle can be effective in other critically ill populations.

Fitness costs in Oxycarenus hyalinipennis Costa (Hemiptera: Lygaeidae) associated with laboratory-selected resistance to imidacloprid

The use of insecticides is widespread for the management of insect pest populations. Injudicious use of insecticides is responsible for rapid development of resistance, environmental pollution and human health problems. Insecticide resistance is a great problem in managing insect pest populations of different crops using insecticides. The evolution of resistance may also affect other fitness parameters of resistant insects. In our study, the impact of imidacloprid resistance development on the fitness parameters of Oxycarenus hyalinipennis Costa (Hemiptera: Lygaeidae) and resistance stability was evaluated. After undergoing 19 generations of development selecting for resistance to imidacloprid, the imidacloprid selected (Imida-Sel) strain of O. hyalinipennis developed 55.30-fold and 146.50-fold resistance compared to UNSEL and susceptible strain, respectively. Imidacloprid resistance was found unstable and the resistant strain reverted towards susceptibility after cessation of insecticide selection pressure for eight generations. The value for Rf (relative fitness) was 0.41 for Imida-Sel with a significant reduction in mean relative growth rate (MRGR), intrinsic rate of natural increase (Rm) and net reproductive rate (Ro). Values of Rf for C1 and C2 were 0.85 and 0.77, respectively. The present study was designed to propose a comprehensive strategy for suppression of O. hyalinipennis. O. hyalinipennis exhibits potential for developing imidacloprid resistance, but the resistance was unstable and manageable with insecticide rotation. In addition, the fitness disadvantage associated with imidacloprid resistance may also slow down field evolution of imidacloprid resistance.

Continuous Glucose Monitoring-Recorded Hypoglycemia with Insulin Degludec or Insulin Glargine U100 in People with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia.

Background and Aims: Nocturnal hypoglycemia is mainly a consequence of inappropriate basal insulin therapy in type 1 diabetes (T1D) and may compromise optimal glycemic control. Insulin degludec is associated with a lower risk of nocturnal hypoglycemia in T1D. As nocturnal hypoglycemia is often asymptomatic, we applied continuous glucose monitoring (CGM) to detect a more precise occurrence of nocturnal hypoglycemia in the HypoDeg trial, comparing insulin degludec with insulin glargine U100 in people with T1D and previous nocturnal severe hypoglycemia. Materials and Methods: In the HypoDeg trial, 149 people with T1D were included in an open-label randomized cross-over trial. Sixty-seven participants accepted optional participation in the predefined substudy of 4 × 6 days of blinded CGM requiring completion of at least one CGM period in each treatment arm. CGM data were reviewed for hypoglycemic events. Results: Treatment with insulin degludec resulted in a relative rate reduction (RRR) of 36% (95% confidence interval [CI]: 10%-54%; P < 0.05) in nocturnal CGM-recorded hypoglycemia (≤3.9 mmol/L), corresponding to an absolute rate reduction (ARR) of 0.85 events per person-week. In nocturnal CGM-recorded hypoglycemia (≤3.0 mmol/L), we found an RRR of 53% (95% CI: 36%-65%; P < 0.001), corresponding to an ARR of 0.75 events per person-week. At the lower detection limit of the CGM (≤2.2 mmol/L), treatment with insulin degludec resulted in a significant RRR of 58% (95% CI: 23%-77%; P = 0.005). The reductions were primarily due to significant RRRs in asymptomatic hypoglycemia. Conclusion: In people with T1D, prone to nocturnal severe hypoglycemia, insulin degludec compared with insulin glargine U100 significantly reduces nocturnal CGM-recorded hypoglycemia. www.clinicaltrials.gov (#NCT02192450).