1st-3rd Quartiles Research Articles

Procedural sedation for direct current cardioversion: a feasibility study between two management strategies in the emergency department

BackgroundA cardiologist-only approach to procedural sedation with midazolam in the setting of elective cardioversion (DCC) for AF has already been proven as safe as sedation with propofol and anaesthesiologist assistance. No data exist regarding the safety of such a strategy during emergency procedures. The aim of this study is to compare the feasibility of sedation with midazolam, administered by a cardiologist, to an anaesthesiologist-assisted protocol with propofol in emergency DCC.MethodsSingle centre, prospective, open blinded, randomized study including all consecutive patients admitted to the Emergency Department requiring urgent or emergency DCC. Patients were randomized in a 1:1 fashion to either propofol or midazolam treatment arm. Patients in the midazolam group were managed by the cardiologist only, while patients treated with propofol group underwent DCC with anaesthesiologist assistance.ResultsSixty-nine patients were enrolled and split into two groups. Eighteen patients (26.1%) experienced peri-procedural adverse events (bradycardia, severe hypotension and severe hypoxia), which were similar between the two groups and all successfully managed by the cardiologist. No deaths, stroke or need for invasive ventilation were registered. Patients treated with propofol experienced a greater decrease in systolic and diastolic blood pressure when compared with those treated with midazolam.As the procedure was shorter when midazolam was used, the median cost of urgent/emergency DCC with midazolam was estimated to be 129.0 € (1st-3rd quartiles 114.6–151.6) and 195.6 € (1st-3rd quartiles 147.3–726.7) with propofol (p < .001).ConclusionsProcedural sedation with midazolam given by the cardiologist alone was feasible, well-tolerated and cost-effective in emergency DCC.

P428Cost-effectiveness of sedation for electrical cardioversion in the emergency department: a subanalysis of the Instead trial

Abstract BACKGROUND Direct current cardioversion (DCCV) represents the most widely used and effective method to restore sinus rhythm in patients with persistent AF. No specific guidelines or recommendations with regards to the most appropriate drug that should be used for procedural sedation have been described. Propofol is one of the most used drugs, however it should be administered only by personnel trained in advanced airway management. Midazolam has been described as a potential alternative. PURPOSOSE The aim of our study was to assess the cost-effectiveness of procedural sedation with midazolam compared to the one with propofol for urgent/emergency DCCV in the emergency department. METHODS Single centre, prospective, open blinded, randomized study including 66 consecutive patients admitted to the emergency department requiring urgent or emergency DCCV for haemodynamic instability, chest pain or symptomatic palpitations. The enrolled patients were randomized in a 1:1 fashion into the propofol or midazolam group. With regards to the propofol group, the procedure was carried out with the assistance of the anaesthesiologist. In the midazolam group, both the procedural sedation and the cardioversion were carried out by the cardiologist alone. RESULTS Thirty-tree patients underwent procedural sedation with propofol and 33 with midazolam. Medical costs included expenses for personnel and related to possible procedural delays. The median medical cost was of 14.9 € for the midazolam group and 46.7 € for the propofol group (p&amp;lt;.001) and was mainly driven by an increased delay and lack of coordination between the cardiologist and the anaesthesiologist. The median material cost in the midazolam group was higher than in the propofol one as the former implied the use of flumazenil (83.7 € vs. 78.8 €, p&amp;lt;.001). Hospitalization costs included the cost related to monitoring time in the emergency department and possible costs derived by the admission to a medical ward. They added up to a median of 28.1 € in the midazolam group and 48.7 for the propofol group (p=.004) as most patients were discharged safely after a few hours. The total median cost of urgent/emergency DCCV with midazolam was estimated to be 126.2 € (1st-3rd quartiles 114.4-142.6) and 203.3 € (1st-3rd quartiles 149.3-734.8) with propofol (p&amp;lt;.001). There was no significant difference in terms of adverse events. Sedation with midazolam was as safe, efficient and tolerated as sedation with propofol. Length of procedure was shorter when midazolam was used compared to propofol usage. Patients who underwent sedation with midazolam were safely discharged earlier. CONCLUSIONS Procedural sedation for electrical cardioversion in the emergency department is more cost-effective than sedation with propofol. By using midazolam we estimated that 77 € are saved for each DCCV. This is driven by the absence of another operator and the possibility of a quicker discharge given the use of flumazenil.

1110-P: Effect of Raised Alanine Transaminase (ALT) Levels on HbA1c in the Association of British Clinical Diabetologists (ABCD) Nationwide Audits of SGLT2 Inhibitors (SGLT2i)

Introduction: Alanine transaminase (ALT) is an important marker for Nonalcoholic Fatty Liver Disease (NAFLD), and its levels are reduced following treatment with SGLT2i. However, how raised ALT levels and hence NAFLD affects HbA1c response to SGLT2i is not known. Methods: Data for this study was obtained from the ABCD nationwide audits of patients with type 2 diabetes started on SGLT2i. We used a gradient boosting machine learning algorithm (GBM) to identify if ALT is an important predictor of glycaemic response to SGLT2i. The results of the GBM model were confirmed using linear regression analysis where the absolute drop in HbA1c was modelled as a dependent variable with baseline ALT as independent variable adjusted for relevant covariates. Results: We studied 9,609 patients initiated on Empagliflozin (n=5061), Dapagliflozin (n=3711) or Canagliflozin (n=837). The mean age of the study population was 59(±10.3), 62% male with a mean weight of 96.6(±18.8), baseline eGFR 81(±11) and baseline HbA1c 9.06% (±1.62). At a median 5.8 months follow-up, the mean HbA1c drop was 0.81% and was similar in all three types of SGLT2i. The drop in HbA1c was 0.62%, 0.78% and 1.01% in 1st 2nd and 3rd quartiles of baseline ALT, respectively (P-Anova &amp;lt;0.0001). In the GBM analysis the important predictors of glycaemic response were baseline weight (relative influence (RI)=71%), and baseline HbA1c (RI= 7.2%), baseline ALT (RI= 5.6%) baseline creatinine (RI= 4.9%). The model accuracy was 0.73 (0.71-0.75) and area under the curve was 0.83. In the linear regression model, higher baseline ALT was associated with a larger drop in HbA1c (beta=0.007, P&amp;lt;0.0001) after adjustments for baseline weight, weight loss, baseline HbA1c, and duration of diabetes. Conclusion: Higher baseline ALT levels are associated with a more significant SGLT2 induced HbA1c drop and SGLT2 inhibitors and are likely to be more effective in those with NAFLD. Disclosure H. Deshmukh: None. A. Bickerton: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. D.K. Sennik: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. K. Adamson: None. M. Yadagiri: None. I.W. Gallen: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. T. Sathyapalan: Research Support; Self; Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; Ipsen Biopharmaceuticals.

Evaluation of the reentry vulnerability index to predict ventricular tachycardia circuits using high-density contact mapping

BackgroundIdentifying arrhythmogenic sites to improve ventricular tachycardia (VT) ablation outcomes remains unresolved. The reentry vulnerability index (RVI) combines activation and repolarization timings to identify sites critical for reentrant arrhythmia initiation without inducing VT.ObjectiveThe purpose of this study was to provide the first assessment of RVI’s capability to identify VT sites of origin using high-density contact mapping and comparison with other activation-repolarization markers of functional substrate.MethodsEighteen VT ablation patients (16 male; 72% ischemic) were studied. Unipolar electrograms were recorded during ventricular pacing and analyzed offline. Activation time (AT), activation–recovery interval (ARI), and repolarization time (RT) were measured. Vulnerability to reentry was mapped based on RVI and spatial distribution of AT, ARI, and RT. The distance from sites identified as vulnerable to reentry to the VT site of origin was measured, with distances <10 mm and >20 mm indicating accurate and inaccurate localization, respectively.ResultsThe origins of 18 VTs (6 entrainment, 12 pace-mapping) were identified. RVI maps included 1012 (408–2098) (median, 1st–3rd quartiles) points per patient. RVI accurately localized 72.2% VT sites of origin, with median distance of 5.1 (3.2–10.1) mm. Inaccurate localization was significantly less frequent for RVI than AT (5.6% vs 33.3%; odds ratio 0.12; P = .035). Compared to RVI, distance to VT sites of origin was significantly larger for sites showing prolonged RT and ARI and were nonsignificantly larger for sites showing highest AT and ARI gradients.ConclusionRVI identifies vulnerable regions closest to VT sites of origin. Activation-repolarization metrics may improve VT substrate delineation and inform novel ablation strategies.

Dose-dependent effects of mandibular advancement on optimal positive airway pressure requirements in obstructive sleep apnoea.

Implementation of mandibular advancement splint (MAS) therapy as first-line treatment for obstructive sleep apnoea (OSA) is hindered by inter-individual variability of treatment outcomes and lack of robust patient selection methods. Optimal continuous positive airway pressure (CPAP) requirement provides an estimate of airway collapsibility severity, and high CPAP requirements predict MAS therapy failure in retrospective studies. Thus, understanding the effects of mandibular advancement on optimal CPAP requirements may enhance optimisation of patient selection for MAS therapy. This study aims to determine dose-dependent effects of mandibular advancement on optimal CPAP requirements in OSA. Prior to MAS therapy initiation, participants with OSA (apnoea-hypopnea index (AHI) > 10 events/h) underwent a research polysomnogram in which a remotely controlled mandibular positioner (RCMP) was used to determine dose-response effects of varying mandibular advancement positions (0% 'habitual bite' and 25, 50, 75 and 100% of maximum mandibular advancement, in random order) on optimal CPAP requirements. A separate polysomnography determined treatment outcome. Data are presented as mean ± SD or median (1st-3rd quartiles). Seventeen participants (age = 47 ± 9years, body mass index = 26kg/m2 (23-27), apnoea-hypopnea index = 18 events/h (14-44) and minimal oxygen saturation = 84 ± 7%) were studied. Optimal CPAP requirements were reduced with mandibular advancement in a dose-dependent manner (8.9 ± 2.4 vs. 7.9 ± 2.8, 6.4 ± 1.8, 5.7 ± 1.9 and 4.9 ± 1.8cmH2O; respectively, p < 0.0001). Compared with non-responders, responders to MAS therapy had lower AHI, lower arousal index and greater MinSaO2 at baseline. Optimal CPAP requirements at 0% mandibular advancement (or other positions) were not different between groups. Increasing mandibular advancement lowers optimal CPAP requirements in a dose-dependent manner. This supports prior work indicating a beneficial effect of MAS on upper airway collapsibility.

Sex-specific differences and survival in patients with idiopathic pulmonary arterial hypertension 2008-2016.

BackgroundWomen with idiopathic pulmonary arterial hypertension (IPAH) have been found to have a worse haemodynamic status at diagnosis, but better survival than men. Over the past decade, demographics have changed and new treatments have become available. The objective of this study was to investigate sex differences in an incident IPAH population diagnosed between 2008 and 2016.MethodsDifferences in clinical characteristics of patients included in the Swedish Pulmonary Arterial Hypertension Register (SPAHR) were analysed at the time of diagnosis. Survival by sex was investigated using Cox proportional hazard regression and Kaplan–Meier curves.ResultsThe study included 271 patients diagnosed with IPAH, median age was 68 (1st–3rd quartiles 54–74) years and 56% were women. At diagnosis, women were younger, had lower pulmonary vascular resistance and fewer comorbidities and more often received a combination of PAH-targeted therapies than men. Men had worse survival rates than women (hazard ratio 1.49; CI 1.02–2.18; p=0.038), but this difference did not remain after adjustment for age (hazard ratio 1.30; CI 0.89–1.90; p=0.178).ConclusionsMen with incident IPAH have worse crude survival than women. This is due to women being younger with a less pronounced comorbidity burden than men at the time of diagnosis.

Low incidence of nephrotoxicity following intravenous administration of iodinated contrast media: a prospective study.

To estimate the incidence of contrast-induced acute kidney injury (CI-AKI) after intravenous (iv) iodinated contrast material (ICM) exposure. This prospective cohort study included all consecutive patients who underwent radiological investigations using low-osmolar iopamidol 370mg/ml in a regional hospital over a period of 36months, without any exclusion criteria. The estimated glomerular filtration rate (eGFR) was evaluated using the MRDR equation before (2-10days) and after (24-36h) radiological investigations. CI-AKI was defined as a ≥ 25% decrease in eGFR from baseline. CI-AKI incidence was estimated using a binomial distribution. The association between CI-AKI and demographic and clinical characteristics was modeled using logistic regression. The study included 1541 patients with a median age of 68 (1st-3rd quartiles 58-76) years with various comorbidities, 30% of whom had pre-existing CKD. Patients affected by stage III or IV chronic kidney disease (CKD) received an infusion of 0.9% normal saline (1.0-1.5ml/kg/h) before and after iso-osmolar iodixanol administration. CI-AKI was observed in 33 patients (2.1%, 95% CI 1.5-3.0). The logistic regression analysis showed that antibiotic and statin therapies were significantly associated with CI-AKI. The probability of developing CI-AKI decreased by 80% in patients taking statins (OR = 0.20, 95% CI 0.03; 0.68) and increased approximately three times in patients with antibiotic therapy compared with those who did not take statins and antibiotics (OR = 2.92, 95% CI 1.21; 6.36). Our data suggest that low-osmolar iopamidol carries a low incidence of nephrotoxicity, even in subjects with various comorbid conditions or reduced renal function. • IV administration of ICM carries a low incidence of nephrotoxicity, which was transient in observed patients. • Statin therapy is negatively associated with AKI in patients exposed to ICM. • Pre-existing impairment of renal function is not associated with AKI in patients exposed to ICM.

Photoplethysmographic characterization of vascular tone mediated changes in arterial pressure: an observational study.

To determine whether a classification based on the contour of the photoplethysmography signal (PPGc) can detect changes in systolic arterial blood pressure (SAP) and vascular tone. Episodes of normotension (SAP 90-140mmHg), hypertension (SAP > 140mmHg) and hypotension (SAP < 90mmHg) were analyzed in 15 cardiac surgery patients. SAP and two surrogates of the vascular tone, systemic vascular resistance (SVR) and vascular compliance (Cvasc = stroke volume/pulse pressure) were compared with PPGc. Changes in PPG amplitude (foot-to-peak distance) and dicrotic notch position were used to define 6 classes taking class III as a normal vascular tone with a notch placed between 20 and 50% of the PPG amplitude. Class I-to-II represented vasoconstriction with notch placed > 50% in a small PPG, while class IV-to-VI described vasodilation with a notch placed < 20% in a tall PPG wave. 190 datasets were analyzed including 61 episodes of hypertension [SAP = 159 (151-170) mmHg (median 1st-3rd quartiles)], 84 of normotension, SAP = 124 (113-131) mmHg and 45 of hypotension SAP = 85(80-87) mmHg. SAP were well correlated with SVR (r = 0.78, p < 0.0001) and Cvasc (r = 0.84, p < 0.0001). The PPG-based classification correlated well with SAP (r = - 0.90, p < 0.0001), SVR (r = - 0.72, p < 0.0001) and Cvasc (r = 0.82, p < 0.0001). The PPGc misclassified 7 out of the 190 episodes, presenting good accuracy (98.4% and 97.8%), sensitivity (100% and 94.9%) and specificity (97.9% and 99.2%) for detecting episodes of hypotension and hypertension, respectively. Changes in arterial pressure and vascular tone were closely related to the proposed classification based on PPG waveform.Clinical Trial Registration NTC02854852.

Uncertainty in Rainfall Intensity Duration Frequency Curves of Peninsular Malaysia under Changing Climate Scenarios

This study developed a methodological framework to update the rainfall intensity-duration-frequency (IDF) curves under climate change scenarios. A model output statistics (MOS) method is used to downscale the daily rainfall of general circulation models (GCMs), and an artificial neural network (ANN) is employed for the disaggregation of projected daily rainfall to hourly maximum rainfall, which is then used for the development of IDF curves. Finally, the 1st quartiles, medians, and 3rd quartiles of projected rainfall intensities are estimated for developing IDF curves with uncertainty level. Eight GCM simulations under two radiative concentration pathways (RCP) scenarios, namely, RCP 4.5 and RCP 8.5, are used in the proposed framework for the projection of IDF curves with related uncertainties for peninsular Malaysia. The projection of rainfall revealed an increase in the annual average rainfall throughout the present century. The comparison of the projected IDF curves for the period 2006–2099 with that obtained using GCM hindcasts for the based period (1971–2005) revealed an increase in rainfall intensity for shorter durations and a decrease for longer durations. The uncertainty in rainfall intensity for different return periods for shorter duration is found to be 2 to 6 times more compared to longer duration rainfall, which indicates that a large increase in rainfall intensity for short durations projected by GCMs is highly uncertain for peninsular Malaysia. The IDF curves developed in this study can be used for the planning of climate resilient urban water storm water management infrastructure in Peninsular Malaysia.

Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study

BackgroundAnti-synthetase (AS) and dermato-pulmonary associated with anti-MDA-5 antibodies (aMDA-5) syndromes are near one of the other autoimmune inflammatory myopathies potentially responsible for severe acute interstitial lung disease. We undertook a 13-year retrospective multicenter study in 35 French ICUs in order to describe the clinical presentation and the outcome of patients admitted to the ICU for acute respiratory failure (ARF) revealing AS or aMDA-5 syndromes.ResultsFrom 2005 to 2017, 47 patients (23 males; median age 60 [1st–3rd quartiles 52–69] years, no comorbidity 85%) were admitted to the ICU for ARF revealing AS (n = 28, 60%) or aMDA-5 (n = 19, 40%) syndromes. Muscular, articular and cutaneous manifestations occurred in 11 patients (23%), 14 (30%) and 20 (43%) patients, respectively. Seventeen of them (36%) had no extra-pulmonary manifestations. C-reactive protein was increased (139 [40–208] mg/L), whereas procalcitonine was not (0.30 [0.12–0.56] ng/mL). Proportion of patients with creatine kinase ≥ 2N was 20% (n = 9/47). Forty-two patients (89%) had ARDS, which was severe in 86%, with a rate of 17% (n = 8/47) of extra-corporeal membrane oxygenation requirement. Proportion of patients who received corticosteroids, cyclophosphamide, rituximab, intravenous immunoglobulins and plasma exchange were 100%, 72%, 15%, 21% and 17%, respectively. ICU and hospital mortality rates were 45% (n = 21/47) and 51% (n = 24/47), respectively. Patients with aMDA-5 dermato-pulmonary syndrome had a higher hospital mortality than those with AS syndrome (n = 16/19, 84% vs. n = 8/28, 29%; p = 0.001).ConclusionsIntensivists should consider inflammatory myopathies as a cause of ARF of unknown origin. Extra-pulmonary manifestations are commonly lacking. Mortality is high, especially in aMDA-5 dermato-pulmonary syndrome.

Extraperitoneal vs. transperitoneal robot-assisted laparoscopic radical prostatectomy-analysis of perioperative outcomes, a single surgeon's experience.

Robot-assisted laparoscopic radical prostatectomy (RRP) has traditionally been done using transperitoneal (TP) approach. This requires patients to be in the steep Trendelenburg position with antecedent risks of high intraoperative ventilatory pressure, post-operative confusion status, corneal and cerebral edema, deep vein thrombosis (DVT), predisposes risk of intestinal injury and slight delay in bowel recovery. Extraperitoneal (EP-RRP) approach circumvents the above given issues. Between July 2013 and October 2016, 57 patients underwent RRP for adenocarcinoma done by a single surgeon (NR). Salvage prostatectomies were excluded. RRP was performed using techniques TP (n = 23) and EP (n = 34). Patients were selected in a non-randomized fashion. Clinico-pathologic parameters and perioperative outcomes were compared in both groups using nonparametric tests. Patient demographics, clinico-pathological features, length of stay and total operative time were similar in both groups. Dock (Trendelenburgh) time was shorter in EP-RRP compared to TP-RRP [median (1st-3rd quartiles) (p value)] [180 (150-220) min vs. 220 (180-230) min (p = 0.039)]. Other significant differences includes EP-RRP vs. TPRRP, ventilatory pressures (cm of H2O) [34 (32-34) vs. 40 (38-40) (p = 0.000)], ETCO2 (mm of Hg) [38 (36-40) vs. 32 (30-34) (p = 0.000)], ambulation (day) [0.00 (0-1) vs. 0.00 (0-2) (p = 0.022)], return of bowel activity (day) [1.0 (1.0-2.0) vs. 2.0 (2.0-2.0) (p = 0.000)] and opening of bowel (day) [2.0 (1.0-2.0) vs. 3.0 (3.0-3.0) (p = 0.000)]. EP-RRP offers similar clinical outcomes to TPRRP but with the advantages of shorter Trendelenburgh time, early recovery of bowel functions with avoidance of bowel injury and intraperitoneal urine leak. Overall, early recovery of patients who had undergone EP-RRP potentiates it to be performed as day care procedure.

Airway responsiveness to methacholine and incidence of COPD: an international prospective cohort study

BackgroundIt has been debated, but not yet established, whether increased airway responsiveness can predict COPD. Recognising this link may help in identifying subjects at risk.ObjectiveWe studied prospectively whether airway responsiveness...

Minimal Use of Opioids for Pain Relief in an Internal Medicine Department.

The objective of the study was to determine if pain control was adequate despite our policy of limited opioid use. In this observational cohort study, we reviewed 300 consecutive patient charts from an internal medicine department. We extracted demographic data, as well as the patients' primary diagnosis, pain on admission, daily pain evaluations (numerical rating score [NRS]), and treatment. Significant pain was defined as a score of ≥3 on the NRS. We determined the incidence of pain and pain control and reviewed the charts of those with an NRS ≥3 for ≥3 days to determine the need for opioid therapy. Of 1692 total hospitalization days in the 300 consecutive patients with a median age of 80 years (1st-3rd quartiles, 65-87 years) there were 204 days with complaints of pain (12.1%) and 149 days (8.8%) with reports of pain of ≥3 on the NRS. Overall, 28.3% (85 of 300) of the patients had significant pain during their hospitalization. Most of the pain, however, (80.0%, 68 of 85) was short-term (1-2 days) whether or not the patient received pain medication. Pain relief treatment in the hospital included opioids in 17 (5.7%, 95% confidence interval [CI] 3.5-8.9) and dipyrone in 36 (12%, 95% CI 8.8-16) of the 300 patients. Pain control was adequate in the seven patients with prolonged pain who did not receive opioids. There were only two patients discharged with prescriptions for opioids (0.7%, 95% CI 0.2-2.6). Significant pain is common in patients hospitalized in an internal medicine department, but the pain is mostly short term and pain control is adequate despite the restricted use of opioid therapy during hospitalization.

Ultrasound B-lines for detection of late lung fibrosis in breast cancer patients after radiation therapy.

Radiation therapy (RT) for breast cancer after conservative surgery can be life-saving but remains associated with significant late side effects, including lung fibrosis, detected by chest CT. Aim of this study was to assess whether lung ultrasound (LUS) may detect late lung fibrosis through the biomarker of B-lines. We evaluated 30 women (median age 67 years, range 46-80 years) about 3-8 years after RT (follow up 38-101 months, median 58 months) for left (n = 12) or right (n = 18) breast cancer (stage 1, n = 24; stage 2, n = 6), treated with total dose 40.5 - 50.00 Gy with/without boost dose). In all, both treated and contralateral hemithorax were evaluated. LUS was performed and B-lines evaluated with a 28-region antero-lateral scan, from second to fifth intercostal spaces, along the mid-axillary, anterior axillary, mid-clavicular, and parasternal lines. In each space, the B-lines were counted from 0 = black lung to 10 = white lung. The sum of B-lines in all spaces generated the B-line score of each hemithorax. Median B-line score was higher in the irradiated site than in the contralateral control hemithorax (9, 1st-3rd quartiles: 2-23 vs 3, 1st-3rd quartiles: 1-4; P < 0.05). In the treated hemithorax, higher mean lung doses ( > median value of 2.7 Gy) were associated with more B-lines when compared to lower doses (< 2.7 Gy): 9 vs 5, p <0.001. RT in female breast cancer survivors is associated with increase in B-lines in the targeted hemithorax, likely due to lung fibrosis, and related to the lung mean dose. LUS can provide a simple "echo-marker" of lung fibrosis.

Prevalence and determinants of vitamin D deficiency in the third trimester of pregnancy: a multicentre study in Switzerland.

Vitamin D deficiency during pregnancy is associated with negative health consequences for mothers and their infants. Data on the vitamin D status of pregnant women in Switzerland are scarce. A three-centre study was conducted in the obstetric departments of Zurich, Bellinzona and Samedan (Switzerland) to investigate the prevalence and determinants of vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D)<50 nmol/l) in 3rd-trimester pregnant women living in Switzerland (n 305), and the correlation between 25(OH)D in pregnant women and their offspring at birth (n 278). Demographic and questionnaire data were used to explore the determinants of vitamin D deficiency. Median concentration of serum 25(OH)D in the third trimester of pregnancy was 46·0 nmol/l (1st-3rd quartiles: 30·5-68·5), representing a 53·4 % prevalence of vitamin D deficiency. 25(OH)D levels in the umbilcal cord blood (median: 50·0 nmol/l; 1st-3rd quartiles: 31·0-76·6) strongly correlated with mothers' serum 25(OH)D (Spearman's correlation ρ=0·79, P<0·001). Multivariable logistic regression analysis showed that significant determinants of vitamin D deficiency in pregnant women were centre of study, country of origin, season of delivery and vitamin D supplement intake. Near-term BMI, skin colour, use of sunscreen and mothers' education, although each not individually significant, collectively improved the ability of the model to explain vitamin D status. Low vitamin D levels were common in this sample of pregnant women and their newborns' cord blood. Vitamin D supplement intake was the most actionable determinant of vitamin D status, suggesting that vitamin D supplementation during pregnancy should receive more attention in clinical practice.

A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study.

While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low. This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints). The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles). Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P=0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P=0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one). In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

Treatment delay and fatal outcomes of pulmonary tuberculosis in advanced age: a retrospective nationwide cohort study

Background and objectiveStudies focusing on pulmonary tuberculosis in advanced age (≥80 years) are lacking. This study aimed to explore treatment delay, outcomes and their predictors in this group.MethodsAdult (≥20 years) patients with pulmonary tuberculosis were identified from the National Health Insurance Research Database of Taiwan from 2004 to 2009. Treatment completion and mortality rates were noted at one year after treatment.ResultsAmong the 81,081 patients with pulmonary tuberculosis identified, 13,923 (17.2%) were aged ≥80 years, and 26,897 (33.2%) were aged 65–79 years. The treatment completion, mortality rates and treatment delay were 54.8%, 34.7% and 61 (12–128) [median, (1st-3rd quartiles)] days in patients aged ≥80 years, 68.3%, 18.5% and 53 (8–122) days in patients aged 65–79 years, and 78.9%, 6.5% and 21 (1–84) days in patients aged <65 years, respectively. The elder patients were more likely to receive second-line anti-tuberculosis agents. The treatment completion rate decreased with older age, female sex, comorbidities, low income, requiring second-line anti-tuberculosis agents, severity of pulmonary tuberculosis and longer treatment delay. Older age, female sex, comorbidities, low income, and not undergoing rapid molecular diagnostic tests were independently associated with longer treatment delays.ConclusionsPulmonary tuberculosis in advanced age has a longer treatment delay and a higher mortality rate. Applying rapid molecular diagnostic tools may reduce treatment delay and should be integrated into the diagnostic algorithm for pulmonary tuberculosis, particularly in elderly patients.

How Did the Dengue Fever Outbreak Progress in Yoyogi Park, Tokyo, in 2014?-Evaluation Based on a Mathematical Model.

In the summer of 2014, an outbreak of autochthonous dengue fever occurred in Yoyogi Park and its vicinity, Tokyo, Japan. In this study, we investigated how the dengue fever outbreak progressed in Yoyogi Park using a mathematical model. This study was limited to the transmission of the dengue virus in Yoyogi Park and its vicinity. We estimated the distributions of the intrinsic incubation period and infection dates on the basis of epidemiological information on the dengue outbreak in 2014. We searched for an assumption that satisfactorily explains the outbreak in 2014 using rough estimates of secondary and tertiary infection cases. We constructed a mathematical model for the transmission of the dengue virus between humans and Aedes albopictus. We carried out 1,000-trial stochastic simulations for all combinations of three kinds of assumption about Ae. albopictus and asymptomatic infection with each of three levels. Simulation results showed that the scale of the outbreak was markedly affected by the daily survival rate of Ae. albopictus. The outbreak involved a small number of secondary infection cases, reached a peak at tertiary infection, and transformed to termination at the fourth infection. Under some assumptions, the daily progress of onset cases was within a range between the 1st-3rd quartiles of 1,000 trials for 87% of dates and within a range between the minimum and maximum for all dates. It is important to execute plans to detect asymptomatic cases and reduce the survival rate of Ae. albopictus to prevent the spread of tertiary infections unless an outbreak is suppressed at the secondary infection stage.

Prediction of excessive weight gain in insulin treated patients with type 2 diabetes.

Weight gain is an ongoing challenge when initiating insulin therapy in patients with type 2 diabetes mellitus (T2DM). However, if prediction of insulin-associated weight gain was possible on an individual level, targeted initiatives could be implemented to reduce weight gain. The aim of the present study was to identify predictors of weight gain in insulin-treated patients with T2DM. In all, 412 individuals with T2DM were, in addition to metformin or placebo, randomized into 18-month treatment groups with three different insulin analog treatment regimens (biphasic, aspart, detemir). Participants with excessive weight gain were defined as the group with weight gain in the 4th quartile (>6.2 kg).We developed a pattern classification method to predict individuals prone to excessive weight gain. Over the 18-month treatment period, median weight gain among all 412 patients was 2.4 kg (95% prediction interval [PI] -5.6, 12.4 kg), whereas median weight gain for those in the upper 4th quartile (n = 103) was 8.9 kg (95% PI 6.3, 15.2 kg). No clinical baseline data were strong predictors of excessive weight gain. However, the weight gain during the first 3 months of the trial and the subsequent dose of insulin yielded a useful predictor for weight gain at the 18-month follow-up. Combining these two predictors into a prediction model with other clinical available information produced a receiver operating characteristic area under the curve of 0.80. We have developed a prediction model that could help identify a substantial proportion of individuals with T2DM prone to large weight gain during insulin therapy.

Complexity analysis of fetal heart rate preceding intrauterine demise

BackgroundVisual non-stress test interpretation lacks the optimal specificity and observer-agreement of an ideal screening tool for intrauterine fetal demise (IUFD) syndrome prevention. Computational methods based on traditional heart rate variability have also been of limited value. Complexity analysis probes properties of the dynamics of physiologic signals that are otherwise not accessible and, therefore, might be useful in this context. ObjectiveTo explore the association between fetal heart rate (FHR) complexity analysis and subsequent IUFD. Our specific hypothesis is that the complexity of the fetal heart rate dynamics is lower in the IUFD group compared with controls. Study designThis case-control study utilized cases of IUFD at a single tertiary-care center among singleton pregnancies with at least 10min of continuous electronic FHR monitoring on at least 2 weekly occasions in the 3 weeks immediately prior to fetal demise. Controls delivered a live singleton beyond 35 weeks’ gestation and were matched to cases by gestational age, testing indication, and maternal age in a 3:1 ratio. FHR data was analyzed using the multiscale entropy (MSE) method to derive their complexity index. In addition, pNNx, a measure of short-term heart rate variability, which in adults is ascribable primarily to cardiac vagal tone modulation, was also computed. Results211 IUFDs occurred during the 9-year period of review, but only 6 met inclusion criteria. The median gestational age at the time of IUFD was 35.5 weeks. Three controls were matched to each case for a total of 24 subjects, and 87 FHR tracings were included for analysis. The median gestational age at the first fetal heart rate tracing was similar between groups (median [1st–3rd quartiles] weeks: IUFD cases: 34.7 (34.4–36.2); controls: 35.3 (34.4–36.1); p=.94). The median complexity of the cases’ tracings was significantly less than the controls’ (12.44 [8.9–16.77] vs. 17.82 [15.21–22.17]; p<.0001). Furthermore, the cases’ median complexity decreased as gestation advanced whereas the controls’ median complexity increased over time. However, this difference was not statistically significant [−0.83 (−2.03 to 0.47) vs. 0.14 (−1.25 to 0.94); p=.62]. The degree of short-term variability of FHR tracings, as measured by the pNN metric, was significantly lower (p<.005) for the controls (1.1 [0.8–1.3]) than the IUFD cases (1.3 [1.1–1.6]). ConclusionsFHR complexity analysis using multiscale entropy analysis may add value to other measures in detecting and monitoring pregnancies at the highest risk for IUFD. The decrease in complexity and short-term variability seen in the IUFD cases may reflect perturbations in neuroautonomic control due to multiple maternal-fetal factors.