Optimal Target Range Research Articles

Optimizing patient safety: Unveiling the significance of cuff pressure in anaesthesia

BackgroundInadequate pressure in the endotracheal tube (ETT) cuff can lead to compromised ventilation or airway injury. Accurate assessment of ETT cuff pressure is essential and should be performed using a manometer, with an optimal target range of 20–30 cmH2O. AimIn this study, we aimed to audit ETT cuff pressures in the operating theatre of our institution, utilizing a manometer from VBM Medizintechnik GmbH™. MethodsFollowing approval from the ethics committee, we conducted an audit from January 2023 to November 2023. A convenience sample was utilized, including adult patients who were intubated in our operating rooms (ORs) during either the morning or afternoon shifts at the time of the audit. ResultsA total of 49 patients were evaluated. Our findings revealed that 78 % of the patients had cuff pressures outside the recommended target range, with recorded pressures ranging from 18 cmH2O to 120 cmH2O, and a mean pressure of 63 cmH2O. Nitrous oxide was not used in any of the cases. Cuff inflation was performed using different syringe volumes: a 5 mL syringe was used in one case, a 10 mL syringe in 20 cases, and a 20 mL syringe in 28 cases, with a mean inflation volume of 9 mL. Statistical analysis indicated no significant difference in ETT cuff pressure related to the type of syringe used or the size of the endotracheal tube. Additionally, no correlation was found between the volume of air used for cuff inflation and the resulting ETT cuff pressure. ConclusionOur audit revealed that only 22 % of the patients had cuff pressures within the recommended limits, highlighting a significant need for increased awareness and education. As maintaining appropriate cuff pressure is a standard of care, systematic implementation of reliable cuff pressure monitoring is strongly recommended.

Hemoglobin (Hgb) Targets in Hemodialysis (HD) Patients: What Is the Optimal Target Range?

Hemoglobin (Hgb) Targets in Hemodialysis (HD) Patients: What Is the Optimal Target Range?

Optimization of anticoagulant therapy in patients undergoing mechanical heart valve replacement

Acquired heart defects have a high prevalence among patients of different age groups and represent a significant social problem. To date, surgery remains the only effective option to treat acquired heart disease, and replacement of the dysfunctional heart valves frequently relies on mechanical prosthetic heart valves which implantation requires lifelong anticoagulant therapy with vitamin K antagonists and constant monitoring of international normalised ratio. However, the optimal target range for international normalised ratio values remains poorly defined. Optimisation of the approaches to anticoagulant therapy for this category of patients is becoming increasingly important. This paper highlights the main problems and possible solutions for patients who have undergone implantation of mechanical heart valves and need constant intake of vitamin K antagonists.

Assessment of health hazards of greenhouse workers considering UV exposure and thermal comfort

Greenhouse (GH) indoor environments are usually manipulated to enhance plant growth and yield, but those environments might not be favorable for GH workers. This study aimed to investigate the health hazards of greenhouse workers from UV radiation exposure and analyze the heat stress and thermal comfort in air-conditioned greenhouses. Two GHs with different covering materials (glass greenhouse-GGH and polycarbonate greenhouse-PCGH) were selected for this study. The UV index of GGH varied from moderate to high (3 to 8) based on the season and deployment of the shade screen, whereas PCGH was always UV risk-free below and above the shade screen. Heat stress was evaluated in terms of wet bulb globe temperature (WBGT) and thermal comfort with the predicted mean vote (PMV) and predicted percent dissatisfied (PPD). The value of WBGT in GGH varied between 17.67 °C and 26.54 °C and between 18.25 °C and 25.97 °C in PCGH. The PMV values ranged from -2.57 to 1.15 for GGH and from -2.24 to 1.42 for PCGH, depending on airspeed, metabolic rate, and indoor conditions. The PPD values ranged between 5.0 to 94.6 % for GGH and 5.0 to 75.0 % for PCGH. As the optimal target range of the indoor environmental parameters (temperature and relative humidity) were maintained in the modern GHs throughout the year, the potential for heat stress and thermal discomfort was not severe. However, as a precaution, avoiding heavy activities around noon is recommended, even in perfectly conditioned greenhouses, which could be above the danger level in low-tech greenhouses.

Glycemic Control in Postoperative Patients in ICU (Comparative Study between Euglycemic Control and Mild Hyperglycemic Control in Patients Outcome)

Abstract Background Hyperglycemia is common complication in postoperative patients admitted to intensive care units, whether a patient has a history of diabetes or not. Hyperglycemia has been associated with increased perioperative morbidity and mortality. Objective To compare between outcome of euglycemia and mild hyperglycemia in postoperative patients admitted to ICU. And achieving the optimal target range for blood glucose in postoperative patients. Patients and Methods We conducted our prospective study on 70 postoperative patients admitted to ICU with blood glucose above 180 mg/dl we managed all of them with intravenous insulin with 2 different blood glucose level targets. Group one with euglycemic control aimed blood glucose level between 110 gm/dl to 140 gm/dl. Group two with mild hyperglycemia aimed blood glucose level target between 140 gm/dl to 180 gm/dl. Results We found in our study that euglycemic control didn’t significantly reduce the postoperative complications and improve the patients outcome in comparison to the mild hyperglycemic group. We also found that there is a mild lower rates of complications in non diabetic patients on euglycemic control compared with those non diabetics treated with mild hypoglycemic targets. Conclusion In our prospective study to compare between effects of euglymic control versus mild hyperglycemia we found that there is no significant difference in patients outcomes between patients controlled at target range 110 gm/dl to 140 gm/dl in comparison to the controlled group between blood glucose range 140 gm/dl to 180 gm/dl in postoperative patients admitted to ICU However there is less complications rates in non diabetics with euglycemic control group in comparison to non diabetics in group two (mild hyperglycemia). The optimal target for blood glucose level is a wide range from 110 mg/dl up to 180 mg/dl.

Diastolic and systolic blood pressure time in target range as a cardiovascular risk marker in patients with type 2 diabetes: A post hoc analysis of ACCORD BP trial

AimsWe investigated the associations between time in target range (TTR) of blood pressure (BP) and cardiovascular outcomes in patients with diabetes. Methods4651 participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) BP trial were included in the present study. The diastolic BP target range was defined as 70 to 80 mm Hg, and the systolic as 120 to 140 mm Hg and 110 to 130 mm Hg for the standard and intensive therapy, respectively. ResultsAfter adjusting for covariates, 1-SD increase of diastolic TTR was significantly associated with lower risks of primary outcome (HR 0.82, 95% CI: 0.74–0.91, P < 0.001; HR 0.86, 95% CI: 0.77–0.95, P = 0.0044, as well as nonfatal myocardial infarction (HR 0.79, 95% CI: 0.69–0.91, P < 0.001). Meanwhile, systolic TTR was significantly associated with various cardiovascular outcomes (P ≤ 0.016) in fully-adjusted models. The diastolic TTR sustained significance in myocardial infarction when systolic blood pressure average was higher than 120 mm Hg. ConclusionsIn patients with diabetes, TTR of diastolic and systolic BP was independently associated with lower risks of major outcomes. The diastolic BP within the optimal target range was considerably important for reducing the risk of myocardial infarction, even when systolic BP was under stable control.

Glycemic Control in Critically Ill COVID-19 Patients: Systematic Review and Meta-Analysis.

Background: Given the mortality risk in COVID-19 patients, it is necessary to estimate the impact of glycemic control on mortality rates among inpatients by designing and implementing evidence-based blood glucose (BG) control methods. There is evidence to suggest that COVID-19 patients with hyperglycemia are at risk of mortality, and glycemic control may improve outcomes. However, the optimal target range of blood glucose levels in critically ill COVID-19 patients remains unclear, and further research is needed to establish the most effective glycemic control strategies in this population. Methods: The investigation was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data sources were drawn from Google Scholar, ResearchGate, PubMed (MEDLINE), Cochrane Library, and Embase databases. Randomized controlled trials, non-randomized controlled trials, retrospective cohort studies, and observational studies with comparison groups specific to tight glycemic control in COVID-19 patients with and without diabetes. Results: Eleven observational studies (26,953 patients hospitalized for COVID-19) were included. The incidence of death was significantly higher among COVID-19 patients diagnosed with diabetes than those without diabetes (OR = 2.70 [2.11, 3.45] at a 95% confidence interval). Incidences of death (OR of 3.76 (3.00, 4.72) at a 95% confidence interval) and complications (OR of 0.88 [0.76, 1.02] at a 95% confidence interval) were also significantly higher for COVID-19 patients with poor glycemic control. Conclusion: These findings suggest that poor glycemic control in critically ill patients leads to an increased mortality rate, infection rate, mechanical ventilation, and prolonged hospitalization.

Non-High-Density Lipoprotein Cholesterol and Cardiovascular Outcomes in Chronic Kidney Disease: Results from KNOW-CKD Study.

As non-high-density lipoprotein cholesterol (non-HDL-C) levels account for all atherogenic lipoproteins, serum non-HDL-C level has been suggested to be a marker for cardiovascular (CV) risk stratification. Therefore, to unveil the association of serum non-HDL-C levels with CV outcomes in patients with non-dialysis chronic kidney disease (ND-CKD), the patients at stages 1 to 5 (n = 2152) from the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD) were prospectively analyzed. The subjects were divided into quintiles by serum non-HDL-C level. The primary outcome was a composite of all-cause death or non-fatal CV events. The median duration of follow-up was 6.940 years. The analysis using the Cox proportional hazard model unveiled that the composite CV event was significantly increased in the 5th quintile (adjusted hazard ratio 2.162, 95% confidence interval 1.174 to 3.981), compared to that of the 3rd quintile. A fully adjusted cubic spline model depicted a non-linear, J-shaped association between non-HDL-C and the risk of a composite CV event. The association remained robust in a series of sensitivity analyses, including the analysis of a cause-specific hazard model. Subgroup analyses reveled that the association is not significantly altered by clinical conditions, including age, gender, body mass index, estimated glomerular filtration rate, and albuminuria. In conclusion, high serum non-HDL-C level increased the risk of adverse CV outcomes among the patients with ND-CKD. Further studies are warranted to define the optimal target range of non-HDL-C levels in this population.

Attitudes of Patients With Chronic Heart Failure Toward Digital Device Data for Self-documentation and Research in Germany: Cross-sectional Survey Study.

BackgroundIn recent years, the use of digital mobile measurement devices (DMMDs) for self-documentation in cardiovascular care in Western industrialized health care systems has increased. For patients with chronic heart failure (cHF), digital self-documentation plays an increasingly important role in self-management. Data from DMMDs can also be integrated into telemonitoring programs or data-intensive medical research to collect and evaluate patient-reported outcome measures through data sharing. However, the implementation of data-intensive devices and data sharing poses several challenges for doctors and patients as well as for the ethical governance of data-driven medical research.ObjectiveThis study aims to explore the potential and challenges of digital device data in cardiology research from patients’ perspectives. Leading research questions of the study concerned the attitudes of patients with cHF toward health-related data collected in the use of digital devices for self-documentation as well as sharing these data and consenting to data sharing for research purposes.MethodsA cross-sectional survey of patients of a research in cardiology was conducted at a German university medical center (N=159) in 2020 (March to July). Eligible participants were German-speaking adult patients with cHF at that center. A pen-and-pencil questionnaire was sent by mail.ResultsMost participants (77/105, 73.3%) approved digital documentation, as they expected the device data to help them observe their body and its functions more objectively. Digital device data were believed to provide cognitive support, both for patients’ self-assessment and doctors’ evaluation of their patients’ current health condition. Interestingly, positive attitudes toward DMMD data providing cognitive support were, in particular, voiced by older patients aged >65 years. However, approximately half of the participants (56/105, 53.3%) also reported difficulty in dealing with self-documented data that lay outside the optimal medical target range. Furthermore, our findings revealed preferences for the self-management of DMMD data disclosed for data-intensive medical research among German patients with cHF, which are best implemented with a dynamic consent model.ConclusionsOur findings provide potentially valuable insights for introducing DMMD in cardiovascular research in the German context. They have several practical implications, such as a high divergence in attitudes among patients with cHF toward different data-receiving organizations as well as a large variance in preferences for the modes of receiving information included in the consenting procedure for data sharing for research. We suggest addressing patients’ multiple views on consenting and data sharing in institutional normative governance frameworks for data-intensive medical research.

Oesophageal safety in voltage-guided atrial fibrillation ablation using ablation index or contact force only: a prospective comparison.

Left atrial ablation using radiofrequency (RF) is associated with endoscopically detected thermal oesophageal lesions (EDELs). The aim of this study was to compare EDEL occurrence after conventional contact force-guided (CFG) RF ablation vs. an ablation index-guided (AIG) approach in clinical routine of voltage-guided ablation (VGA). Predictors of EDEL were also assessed. This study compared CFG (n = 100) with AIG (n = 100) in consecutive atrial fibrillation ablation procedures, in which both pulmonary vein isolation and VGA were performed. In the AIG group, AI targets were ≥500 anteriorly and ≥350-400 posteriorly. Upper endoscopy was performed after ablation.The CFG and AIG groups had comparable baseline characteristics. The EDEL occurred in 6 and 5% (P = 0.86) in the CFG and AIG groups, respectively. Category 2 lesions occurred in 4 and 2% (P = 0.68), respectively. All EDEL healed under proton pump inhibitor therapy. The AI > 520 was the only predictor of EDEL [odds ratio (OR) 3.84; P = 0.039]. The more extensive Category 2 lesions were predicted by: AI max > 520 during posterior ablation (OR 7.05; P = 0.042), application of posterior or roof lines (OR 5.19; P = 0.039), existence of cardiomyopathy (OR 4.93; P = 0.047), and CHA2DS2-VASc score (OR 1.71; P = 0.044). The only Category 2 lesion with AI max < 520 (467) occurred in a patient with low body mass index. Both methods were comparable with respect to clinical complications and EDEL. In consideration of previous reconnection data and our study results regarding oesophageal safety, optimal AI target range might be between 400 and 450.

Inter‐ and intra‐individual concentrations of direct oral anticoagulants: The KIDOAC study

BackgroundDirect oral anticoagulants (DOACs) do not require concentration monitoring. However, whether DOAC concentrations are stable and their variation between and within patients is not well studied. MethodsPatients on vitamin K antagonists (VKA) who switched to rivaroxaban, apixaban, or dabigatran were included between 2018 and 2020. Blood was drawn at DOAC trough and peak concentrations at week 0, 2, and 8. Plasma drug concentrations were determined by anti‐factor Xa concentrations (rivaroxaban, apixaban) or diluted thrombin time (dabigatran). Inter‐ and intra‐individual variability was assessed by calculating the coefficient of variation (CV). Linear regression models were employed to evaluate associations between DOAC trough concentrations and previous VKA dosage, creatinine clearance, and body mass index (BMI). ResultsOne hundred fifty‐two patients were included, of whom 96 (63%) were male and with a mean age of 73.9 ± 8.4 years. For the inter‐individual variability, the CV ranged between 48% and 81% for trough values and between 25% and 69% for peak values among patients using the recommended DOAC dose. Intra‐individual variability was substantially lower, as here the CV ranged between 18% and 33% for trough values and between 15% and 29% for peak values among patients using the recommended DOAC dose. Previous VKA dosage and creatinine clearance were inversely associated with DOAC trough concentrations. No association was found between BMI and DOAC trough concentrations. ConclusionInter‐individual variability of DOAC concentrations was higher than intra‐individual variability. Lower previous VKA dosage and creatinine clearance were associated with higher DOAC trough concentrations. These findings support further study into an optimal target range, in which the risks of both bleeding and thrombosis are minimal.

Impact of blood pressure on coronary perfusion and valvular hemodynamics after aortic valve replacement.

Our objective was to evaluate the impact of various blood pressures (BPs) on coronary perfusion and valvular hemodynamics following aortic valve replacement (AVR). Lower systolic and diastolic (SBP/DBP) pressures from the recommended optimal target range of SBP < 120-130 mmHg and DBP < 80 mmHg after AVR have been independently associated with increased cardiovascular and all-cause mortality. The hemodynamic assessment of a 26 mm SAPIEN 3 transcatheter aortic valve (TAV), 29 mm Evolut R TAV, and 25 mm Magna Ease surgical aortic valve (SAV) was performed in a pulsed left heart simulator with varying SBP, DBP, and heart rate (HR) conditions (60 and 120 bpm) at 5 L/min cardiac output (CO). Average coronary flow (CF), effective orifice areas (EOAs), and valvulo-arterial impedance (Zva) were calculated. At HR of 60 bpm, at SBP < 120 mmHg and DBP < 60 mmHg, CF decreased below the physiological lower limit with several different valves. Zva and EOA were found to increase and decrease respectively with increasing SBP and DBP. The same results were found with an HR of 120 bpm. The trends of CF variation with BP were similar in all valves however the drop below the lower physiological CF limit was valve dependent. In a controlled in vitro system, with different aortic valve prostheses in place, CF decreased below the physiologic minimum when SBP and DBP were in the range targeted by blood pressure guidelines. Combined with recent observations from patients treated with AVR, these findings underscore the need for additional studies to identify the optimal BP in patients treated with AVR for AS.

Optimizing anticoagulation for patients receiving Impella support.

Anticoagulation of patients treated with the Impella percutaneous mechanical circulatory support (MCS) devices is complex and lacks consistency across centers, potentially increasing the risk of complications. In order to optimize safety and efficacy, an expert committee synthesized all available evidence evaluating anticoagulation for patients receiving Impella support in order to provide consensus recommendations for the management of anticoagulation with these devices. The evidence synthesis led to the creation of 42 recommendations to improve anticoagulation management related to the use of the Impella devices. Recommendations address purge solution management, intravenous anticoagulation, monitoring, evaluation and management of heparin-induced thrombocytopenia (HIT), and management during combination MCS support. The use of a heparinized, dextrose-containing purge solution is critical for optimal device function, and a bicarbonate-based purge solution may be an alternative in certain situations. Likewise, intravenous (ie, systemic) anticoagulation with heparin is often necessary, although evidence supporting the optimal assay and target range for monitoring the level of anticoagulation is generally lacking. Patients treated with an Impella MCS device may develop HIT, which is more difficult to evaluate and treat in this setting. Lastly, the use of Impella with extracorporeal membrane oxygenation or for biventricular support creates additional anticoagulation challenges.

Frequency of Achieving Target INR in Patient on Warfarin for Atrial Fibrillation

Background: Warfarin has long been established as the oral anticoagulant of choice. The benefits of warfarin depend on maintaining the International Normalized Ratio (INR). It has been shown that the optimal INR target range is 2-3 for AF patients. Very less number of patients had been reported to achieve and remain in that target INR range. The prevalence of AF in the general population is about 1.6% in women and 2.4% in men and is generally lower in Asian countries Aim: To determine the frequency of achieving target INR in patient on warfarin for atrial fibrillation. Methodology: This is cross sectional study conducted at national institute of cardio vascular disease, Karachi from 31st May 2016 30th November 2016.The sample size of the study were 111, and nonprobability convenience sampling technique was used. Results: Among study population 61 (54.9%) were male and 50(45%) female patients. Mean duration of atrial fibrillation was 3.44±0.97 years. The mean duration of warfarin taken was 11.34±3.96 months. INR (2-3) target achieved in 72(64.9%) patients. Significant association of achieved INR target was observed with duration of atrial fibrillation, duration of warfarin, hypertension, stroke, and Left ventricular dysfunction. Conclusion: Target of INR was achieved in 64.9% patients when these patients were given warfarin doses of 5.0 to 7.5 mg/day. Keywords: Achieving Target INR, Warfarin, Atrial Fibrillation.

The effects of heat on the physical and spectral properties of bloodstains at arson scenes

This study examines the spectral characteristics of blood after being exposed to intense heat within a structural fire. Fire and intense heat have previously been understood to destroy or chemically change bloodstain evidence so that traditional forensic science recovery techniques are rendered ineffectual. Understanding the effects of the denaturation process and physical changes that occur to blood when exposed to heat may develop innovative forensic investigation methods, including the use of reflected infrared photography to enhance the recording of bloodstains. This research revealed that the denaturation of blood, specifically changes to the haemoglobin state from oxyhaemoglobin to methaemoglobin, resulted in the heat affected blood having a more optimal spectral target range within the infrared region when exposed to heat> 200 °C. It was observed both qualitatively and quantitatively using spectrophotometry, that there is a relationship between the appearance, viscosity and infrared absorption properties of blood when exposed to different temperatures as experienced in fire. This result indicated the increased potential for reflected infrared photography to be utilised as an effective tool for crime scene evidence recovery of bloodstains from arson scenes involving fire.

Office Blood Pressure Range and Cardiovascular Events in Patients With Hypertension: A Nationwide Cohort Study in South Korea

BackgroundIt is unclear what office blood pressure (BP) is the optimal treatment target range in patients with hypertension.Methods and ResultsUsing the Korean National Health Insurance Service database, we extracted the data on 479 359 patients with hypertension with available BP measurements and no history of cardiovascular events from 2002 to 2011. The study end point was major cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, or stroke. This cohort study evaluated the association of BP levels (<120/<70, 120–129/70–79, 130–139/80–89, 140–149/90–99, and ≥150/≥100 mm Hg) with MACE. During a median follow‐up of 9 years, 55 401 MACE were documented in our cohort. The risk of MACE was the lowest (adjusted hazard ratio [HR], 0.79; 95% CI, 0.76–0.84) at BP level of <120/<70 mm Hg, and was the highest (HR, 1.32; 95% CI, 1.29–1.36) at ≥150/≥100 mm Hg in comparison with 130 to 139/80 to 89 mm Hg. These results were consistent in all age groups and both sexes. Among patients treated with antihypertensive medication (n=237 592, 49.5%), in comparison with a BP level of 130 to 139/80 to 89 mm Hg, the risk of MACE was significantly higher in patients with elevated BP (≥140/≥90 mm Hg), but not significantly lower in patients with BP of <130/<80 mm Hg. Low BP <120/70 mm Hg was associated with increased risk of all‐cause or cardiovascular death in all age groups.ConclusionsBP level is significantly correlated with the risk of MACE in all Korean patients with hypertension. However, there were no additional benefits for MACE amongst those treated for hypertension with BP <120/70 mm Hg.

Low-density lipoprotein cholesterol &amp;lt;50 mg/dL is an appropriate target after acute coronary syndrome: propensity score-matched analysis of the ODYSSEY OUTCOMES trial

Abstract Background New ESC/EAS guidelines advise a low-density lipoprotein cholesterol (LDL-C) target level &amp;lt;55 mg/dL for patients with acute coronary syndromes (ACS), and a level &amp;lt;40 mg/dL for those with recurrent events. Previous analyses of clinical trials have sought to define an optimal LDL-C target range to prevent major adverse cardiovascular events (MACE). However, those analyses are limited because patients who achieve lower versus higher LDL-C levels on lipid-lowering therapy differ in other characteristics that are prognostic for MACE, including baseline LDL-C, lipoprotein(a), and medication adherence. Aim To overcome these limitations, we performed a propensity score-matching (PSM) analysis of the ODYSSEY OUTCOMES trial, which compared the PCSK9 inhibitor alirocumab with placebo in 18,924 patients with recent ACS. Methods Patients on alirocumab were classified in 1 of 3 pre-specified categories according to Month 4 LDL-C &amp;lt;25 (n=3357), 25–50 (n=3692) or &amp;gt;50 mg/dL (n=2197). Within each category, MACE after Month 4 was compared with patients on placebo using 1:1 PSM on demographic, clinical, and adherence variables. Because the trial design involved blinded substitution of placebo for alirocumab when consecutive LDL-C levels were &amp;lt;15 mg/dL on alirocumab, we also evaluated MACE in those patients (n=730) in comparison with patients chosen from the placebo group by 1:3 PSM. Results Patients in the three achieved LDL-C categories of the alirocumab group differed by baseline age, sex, geographic region; history of diabetes, smoking, peripheral artery disease, cerebrovascular disease, coronary revascularization, heart failure, obstructive pulmonary disease, or malignancy; type of index ACS event; baseline LDL-C, lipoprotein(a), estimated glomerular filtration rate, body mass index, systolic blood pressure; use of intensive statin therapy; and adherence with study medication. After PSM, patients in each LDL-C category on alirocumab were well matched to patients on placebo for these characteristics. Treatment hazard ratios (HRs) for MACE (Figure) were similar in those with achieved LDL-C &amp;lt;25 mg/dL or 25–50 mg/dL. Patients with achieved LDL-C &amp;gt;50 mg/dL achieved less benefit. Patients who achieved consecutive LDL-C levels &amp;lt;15 mg/dL and were switched to placebo nonetheless had a robust HR (0.71, 95% CI 0.52–0.98) and thus did not dilute efficacy of alirocumab among those in the &amp;lt;25 mg/dL achieved LDL-C category. Conclusion After accounting for differences in baseline characteristics and adherence, reduction in risk of MACE with alirocumab was similar in patients who achieved LDL-C &amp;lt;25 or 25–50 mg/dL. These data suggest that an LDL-C target of less than 50 mg/dL may be reasonable after ACS and is essentially congruent with new ESC/EAS guidelines. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi and Regeneron Pharmaceuticals, Inc

Mitigation of the Interplay Effects of Combining 4D Robust With Layer Repainting Techniques in Proton-Based SBRT for Patients With Early-Stage Non-small Cell Lung Cancer.

ObjectiveThe objective of this study was to evaluate the interplay effects in proton-based stereotactic body radiotherapy (SBRT) using 4D robust optimization combined with iso-energy layer repainting techniques for non-small cell lung cancer (NSCLC).Materials and MethodsTwelve patients with early-stage NSCLC who underwent 4DCT were retrospectively selected. A robust CTV-based 4D plan was generated for each based on commercial Treatment planning system (TPS), considering patient setup errors, range uncertainties, and organ motion. The 4D static dose (4DSD) and 4D dynamic dose (4DDD) were calculated using a hybrid deformable algorithm and simulated proton delivery system. An index was developed to quantitatively evaluate the interplay effects. The interplay effects of the 4D robust plan and multiple iso-energy layers (3, 4, 5, 6, and 7) of the robust repainting 4D plan were calculated based on to select the optimal times for layer repainting.ResultsDue to the interplay effects, the mean target values D2 and D5 increased to 1.28 and 1.01%, and the target values D98 and D95 decreased to 2.01 and 1.77%, respectively, for the 4D Robust SBRT plan. After multiple iso-energy repainting times, the interplay effects of the target values D98 and D95 tended to migrate, from 2.01 to 0.92% in target value D98 and from 1.77 to 0.89% in target value D95, respectively. Moreover, a positive linear correlation was observed between the optimal interplay effect mitigation and target range of motion.ConclusionIn proton-based 4D Robust SBRT, the interplay effects degraded the target dose distribution but were mitigated using iso-energy layer repainting techniques. However, there was no significant correlation between the number of repainting layers and improvements in the dose distributions. The optimal layer repainting times based on the interplay effect index were ascertained according to the patient characteristics.

Does permissive hypercapnia carry increased risk for neurodevelopmental sequelae?

Commentary on: Thome UH, Genzel-Boroviczeny O, Bohnhorst B, for the PHELBI Study Group, et al. Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2 targets: the PHELBI follow-up study. Arch Dis Child Fetal Neonatal Ed 2017; 102: F376–82. PMID: 28087725. Despite advances in ventilatory support, it is not clear what levels of PaCO2 are safe in extremely premature infants. Permissive hypercapnia is a strategy that tolerates higher levels of PaCO2 with the expectation to reduce ventilator-induced lung injury. One potential downside of permissive hypercapnia is the association with intraventricular haemorrhages (IVH) and poor developmental outcomes 1, 2. In the PHELBI trial 3, investigators studied the effects of permissive hypercapnia. Although the study had some limitations 4 and was stopped early due to no reduction in BPD or death, it remains a valuable study, showing that hypercapnia did not increase IVH or retinopathy of prematurity (ROP). Investigators assessed neurodevelopment at two years corrected age on infants who participated in the original trial 4. Follow-up evaluations were performed using German translations of accepted standard of care evaluation methods. Age and growth at the follow-up examinations were similar and not suggestive of confounding effects. Neurodevelopment of infants that participated in follow-up assessment was comparable between PaCO2 target groups. Child's development per CDI questionnaire and cerebral palsy were evenly distributed, as well as rates of hearing or visual impairment. This study is limited as the original trial was not designed for detecting neurodevelopmental differences at two-year follow-up and the trial was stopped early after no evidence of treatment effect. Finally, 15% of infants were lost to follow-up (14% in High Target Group and 15% in Low Target Group) and 10% did not complete all follow-up examinations. Baseline characteristics of patients lost to follow-up and those who completed testing appeared similar; however, it would be beneficial for interpretation to see the characteristics of those who did not complete testing. The authors acknowledge that there is no formal German validation for the BSIDII, though results obtained are similar to American infants. There was no blinding to study arm allocation in the original trial, and masking of individuals involved in the neurodevelopmental follow-up testing is not specified. Conclusions drawn from these data must be considered in light of these limitations. Benefits of permissive hypercapnia, as defined by this trial, were not observed in the study findings. BPD is associated with adverse neurodevelopment 5, and optimal PaCO2 levels remain unclear. Observational studies have found that large fluctuations and higher than average PaCO2 increase risk 3, 6, 7, while a meta-analysis of randomised trials for permissive hypercapnia shows that morbidity and neurodevelopmental outcomes did not differ between PaCO2 target groups 8. The PHELBI trial did not identify the optimal target range of PaCO2, and data suggest that permissive hypercapnia does not grant lung protection in extremely low birthweight infants. One should consider that permissive hypercapnia as a strategy to decrease chronic lung disease is not supported by data from this randomised trial. However, based on the comparable neurologic development observed in the study, clinician angst is not warranted and aggressive ventilator adjustments should not be implemented in order to normalise PaCO2 in extremely premature patients who are otherwise clinically stable. https://ebneo.org/2019/06/permissive-hypercapnia-neurodevelopmental-sequelae There was no funding for this review. The authors have no conflicts of interest to disclose.

MS # 20171964 / van den Heuvel - Goldilocks in the NICU—can oxygen be titrated “just right?”

Oxygen is the most commonly used “drug” for preterm infants, and recent large clinical trials highlight the need for careful titration within a narrow therapeutic window. In particular, lower achieved oxygen saturations are associated with increased mortality in extremely preterm infants, possibly due to more time spent in extreme hypoxemia. Automated systems that adjust the inspired oxygen based on the detected O2 saturation are a timely innovation that should improve the ease and precision of maintaining oxygenation within the desired range. Using an automated system, van den Heuvel et al found that a “narrow” target range for O2 saturation (88-92%) did not improve the time spent in the desired saturation range of 86-94%. However, the narrow range did reduce the time spent in moderate and severe hypoxemia (SpO2 <80%) and reduced the number of prolonged episodes of severe hypoxemia. Either approach was superior to manual adjustment and reduced time spent in hyperoxemia (Figure). The task of oxygen titration tends to fall on the shoulders of the busiest caregiver, the bedside nurse. Automated systems appear to go beyond relieving this burden to improve the precision and safety of oxygen therapy. Article page 36 ▶ Optimal Target Range of Closed-Loop Inspired Oxygen Support in Preterm Infants: A Randomized Cross-Over StudyThe Journal of PediatricsVol. 197PreviewTo investigate the effect of different pulse oximetry (SpO2) target range settings during automated fraction of inspired oxygen control (A-FiO2) on time spent within a clinically set SpO2 alarm range in oxygen-dependent infants on noninvasive respiratory support. Full-Text PDF