To Explore a Representative Hypoxic Parameter to Predict the Treatment Response and Prognosis Obtained by [<Superscript>18</Superscript>F]FMISO-PET in Patients with Non-small Cell Lung Cancer

Purpose

To explore a representative hypoxic parameter to predict the treatment response and prognosis for [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO) positron emission tomography (PET)/X-ray computed tomography (CT) in patients with non-small cell lung cancer (NSCLC).

Procedures

Twenty-nine patients with NSCLC underwent FMISO-PET scans before chemoradiotherapy (CRT). The maximum standard uptake values (SUVmax) in the tumor, normal lung, aortic arch, and vertical ridge muscle were measured, and the tumor-to-lung (T/L) ratios, tumor-to-blood (T/B) ratios, ands tumor-to-muscle (T/M) ratios were calculated and analyzed. Fractional hypoxic volume (FHV) was expressed as percentage of hypoxic volume.

Results

SUVmax, T/L ratio, T/B ratio, and FHV were all significantly different between the responders and the non-responders (SUVmax, 2.07?±?0.53 vs. 2.61?±?0.69, P?=?0.026; T/L ratio, 3.16?±?0.85 vs. 4.09?±?1.46, P?=?0.047; T/B ratio, 1.27?±?0.20 vs. 1.48?±?0.32, P?=?0.042; 38.92?±?18.47 vs. 52.91?±?11.29 %, P?=?0.020). However, the T/M ratio was not significantly different between the two populations (1.46?±?0.31 vs. 1.67?±?0.33, P?=?0.098). The correlation ratio between hypoxic parameters and treatment responses ranged from high to low as FHV (r?=?0.412); SUVmax (r?=?0.400); T/L ratio (r?=?0.379), P?<?0.05; and T/B ratio (r?=?0.355), P?=?0.059. According to the area under curve (AUC) to predict response, the hypoxic parameters were arranged as FHV (AUC?=?0.748), SUVmax (AUC?=?0.731), T/L ratio (AUC?=?0.719), and T/B ratio (AUC?=?0.705). Binary logistic regression analyses showed that FHV was the only independent predictor for treatment response with the P value of 0.038. In the progression-free survival (PFS) prediction, both FHV and SUVmax reached statistical significance by Kaplan–Meier plots (FHV, 46.99 %, P?=?0.010; SUVmax, 1.99, P?=?0.046) while only FHV was the independent prognostic factor in multivariate analysis by Cox proportional hazard model (P?=?0.037).

Conclusion

FHV may be a representative hypoxic parameter to predict the CRT response and PFS in patients with NSCLC.

     

Health-related outcomes of critically ill patients with and without sepsis

Purpose

To determine differences in health-related quality of life (HRQoL), survival and healthcare resource use of critically ill adults with and without sepsis.

Methods

We conducted a primary propensity score matched analysis of patients with and without sepsis enrolled in a large multicentre clinical trial. Outcomes included HRQoL at 6 months, survival to 2 years, length of ICU and hospital admission and cost of ICU and hospital treatment to 2 years.

Results

We obtained linked data for 3442 (97.3%) of 3537 eligible patients and matched 806/905 (89.0%) patients with sepsis with 806/2537 (31.7%) without. After matching, there were no significant differences in the proportion of survivors with and without sepsis reporting problems with mobility (37.8% vs. 38.7%, p?=?0.86), self-care (24.7% vs. 26.0%, p?=?0.44), usual activities (44.5% vs. 46.8%, p?=?0.28), pain/discomfort (42.4% vs. 41.6%, p?=?0.54) and anxiety/depression (36.9% vs. 37.7%, p?=?0.68). There was no significant difference in survival at 2 years: 482/792 (60.9%) vs. 485/799 (60.7%) (HR 1.01, 95% CI 0.86–1.18, p?=?0.94). The initial ICU and hospital admission were longer for patients with sepsis: 10.1?±?11.9 vs. 8.0?±?9.8 days (p?<?0.0001) and 22.8?±?21.2 vs. 19.1?±?19.0 days, (p?=?0.0003) respectively. The cost of ICU admissions was higher for patients with sepsis: A$43,345?±?46,263 (€35,109?±?35,043) versus 34,844?±?38,281 (€28,223?±?31,007), mean difference $8501 (€6885), 95% CI $4342–12,660 (€3517?±?10,254), p?<?0.001 as was the total cost of hospital treatment to 2 years: A$74,120?±?60,750 (€60,037?±?49,207) versus A$65,806?±?59,856 (€53,302?±?48,483), p?=?0.005.

Conclusions

Critically ill patients with sepsis have higher healthcare resource use and costs but similar survival and HRQoL compared to matched patients without sepsis.

     

Efficacy of Phonosurgery,Logopedic Voice Treatment and Vocal Pedagogy in Common Voice Problems of Singers

Introduction

Functional and organic impairments of the singing voice are common career-threatening problems of singers presenting in phoniatric and laryngological departments. The objective was to evaluate the efficacy of phonosurgery, logopedic voice treatment and vocal pedagogy in common organic and functional voice problems of singers, including investigation of the recently introduced parameter vocal extent measure (VEM).

Methods

In a prospective clinical study, the analysis of treatment outcome in 76 singers [57 female, 19 male; 38?±?11 years (mean?±?SD)] was based on pre- and post-therapeutic voice function diagnostics and videolaryngostroboscopy. Examination instruments included auditory-perceptual voice assessment, voice range profile (VRP), the VEM calculated from area and shape of the VRP, acoustic–aerodynamic analysis, and patients’ self-assessment (e.g., Singing Voice Handicap Index).

Results

While 28% of all singers (21/76) presented with functional dysphonia, 72% (55/76) were diagnosed with organic vocal fold changes, of which marginal edema (n?=?25), nodules (n?=?9), and polyps (n?=?8) were the most common pathologic changes. Of the 76 singers, 57% (43) received phonosurgery, 43% (33) had conservative pedagogic (14) and logopedic (19) treatment. Three months post-therapeutically, most parameters had significantly improved. The dysphonia severity index (DSI) increased on average from 6.1?±?2.0 to 7.4?±?1.8 (p?<?0.001), and the VEM from 113?±?20 to 124?±?14 (p?<?0.001). Both parameters correlated significantly with each other (r_s?=?0.41). Phonosurgery had the largest impact on the improvement of vocal function. Conservative therapies provided smaller quantitative enhancements but also qualitative vocal restoration with recovered artistic capabilities.

Conclusions

Depending on individual medical indication, phonosurgery, logopedic treatment and voice teaching are all effective, objectively and subjectively satisfactory therapies to improve the impaired singing voice. The use of VEM in singers with functional and organic dysphonia objectifies and quantifies their vocal capacity as documented in the VRP. Complementing the established DSI, VEM introduction into practical objective voice diagnostics is appropriate and desirable especially for the treatment of singers.

     

Increased nitroglycerin-mediated vasodilation in migraineurs without aura in the interictal period

Purpose

Migraine is associated with vascular disorders, but the underlying mechanism is unknown. Nitric oxide (NO) sensitivity is believed to play a major role in migraine pathophysiology. We investigated flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation (NMD) of the brachial artery by means of a key molecular mediator, NO, in patients with migraine without aura in the interictal period whether the abnormality is found.

Methods

A total of 12 patients with migraine without aura and 12 matched healthy controls were enrolled in this study. FMD and NMD were measured in all patients and controls using brachial artery ultrasonography.

Results

There was no significant difference in brachial artery diameter between migraineurs and nonmigraineurs (3.39?±?0.68 vs 3.89?±?0.67 mm, respectively; p?=?0.083). A significant difference in FMD was not found between migraineurs and nonmigraineurs (6.94?±?5.72 vs 6.08?±?2.98%, respectively; p?=?0.651). However, NMD in migraineurs was significant higher than that in nonmigraineurs (21.56?±?7.36 vs 14.23?±?7.41%, respectively; p?=?0.024).

Conclusion

We think that patients with migraine without aura in the interictal period have selective sensitivity in dilator response to nitroglycerin and may have systemic NO sensitivity.

     

Estimation of weight in adults from height: a novel option for a quick bedside technique

Purpose

In critical care situations, there are often neither the means nor the time to weigh each patient before administering strict weight-based drugs/procedures. A convenient, quick and accurate method is a priority in such circumstances for safety and effectiveness in emergent interventions as none exists in adults while those available are complex and yet to be validated. We aimed to study the correlation and accuracy of a quick bedside method of weight estimation in adults using height.

Method

The technique is estimated body weight—eBW(kg)?=?(N ??1)100, where ‘N’ is the measured height in metres.Adult undergraduates were enrolled 10/09/2015. Their heights and weights were measured while the formula was used to obtain the estimated weight. The SPSS version 21.0, Chicago, IL, USA was utilised for data analysis.

Results

We analysed 122 participants aged 21–38?years with height?=?1.55?m–1.95?m. The actual body weight range?=?48.0?kg–91.0 kg, mean?=?65.3?kg?±?9.7?kg and S.E.?=?2.0 while eBW?=?55 kg–95 kg, mean?=?69.1?kg?±?8.4?kg and S.E.?=?1.5. On BMI classes, a positive predictive value of 94.7% for the ‘normal’ category and 95.5% for ‘overweight’.Correlation coefficient at 99% confidence interval yielded (r)?=?+?1, (P?=?0.000) while the linear regression coefficient (r²)?=?+?1 at 95% confidence interval (P?=?0.000).The strength of agreement/precision was established by the Bland-Altman plot at 95%?±?2?s (P?=?0.000) and kappa statistic with value?=?0. 618.

Conclusion

This unprecedented statistical characterisation of the two weight estimate measures to have a good agreement scientifically proposes the utility of our method with the formula eBW(kg)?=?100(N?1) in critical care and ATLS protocol.

     

Left Atrial structure and function in hypertrophic cardiomyopathy sarcomere mutation carriers with and without left ventricular hypertrophy

Background

Impaired left atrial (LA) function is an early marker of cardiac dysfunction and predictor of adverse cardiac events. Herein, we assess LA structure and function in hypertrophy in hypertrophic cardiomyopathy (HCM) sarcomere mutation carriers with and without left ventricular hypertrophy (LVH).

Method

Seventy-three participants of the HCMNet study who underwent cardiovascular magnetic resonance (CMR) imaging were studied, including mutation carriers with overt HCM (n =?34), preclinical mutation carriers without HCM (n =?24) and healthy, familial controls (n =?15).

Results

LA volumes were similar between preclinical, control and overt HCM cohorts after covariate adjustment. However, there was evidence of impaired LA function with decreased LA total emptying function in both preclinical (64?±?8%) and overt HCM (59?±?10%), compared with controls (70?±?7%; p =?0.002 and p =?0.005, respectively). LA passive emptying function was also decreased in overt HCM (35?±?11%) compared with controls (47?±?10%; p =?0.006). Both LAtotal emptying function and LA passive emptying function were inversely correlated with the extent of late gadolinium enhancement (LGE; p?=?0.005 and p <?0.05, respectively), LV mass (p =?0.02 and p <?0.001) and interventricular septal thickness (p?<?0.001 for both) and serum NT-proBNP levels (p?<?0.001 for both).

Conclusion

LA dysfunction is detectable by CMR in preclinical HCM mutation carriers despite non-distinguishable LV wall thickness and LA volume. LA function appears most impaired in subjects with overt HCM and a greater extent of LV fibrosis.

     

Effects of Tiotropium Combined with Theophylline on Stable COPD Patients of Group B,D and its Impact on Small Airway Function: A Randomized Controlled Trial

Introduction

Tiotropium bromide has been widely used in clinical practice, while theophylline is another treatment option for chronic obstructive pulmonary disease (COPD). However, only a few relevant studies have investigated the long-term outcomes and efficacy of both in patients with COPD. We evaluated the effects of tiotropium and low-dose theophylline on stable COPD patients of groups B and D.

Methods

Eligible participants (n?=?170) were randomized and received either tiotropium 18 µg once daily with theophylline 100 mg twice daily (Group I) or tiotropium 18 µg once daily (Group II) for 6 months. COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scores and pulmonary function tests were measured before randomization and during the treatment.

Results

After 6 months of treatment, the CAT scores in both groups decreased significantly (11.41?±?3.56 and 11.08?±?3.05, p?<?0.0001). The changes of CAT (p?=?0.028) and mMRC scores (p?=?0.049) between the two groups differed after 1 month of treatment. In Group I, forced expiratory flow after 25% of the FVC% predicted (MEF₂₅% pred) was significantly improved after 3 months (4.84?±?8.73%, p?<?0.0001) and 6 months (6.21?±?8.65%, p?<?0.0001). There was a significant difference in small airway function tests (MEF₅₀% pred, MEF₂₅% pred, and MMEF% pred) between the two groups after 6 month of treatment (p?=?0.003, p?<?0.0001, and p?=?0.021, respectively).

Conclusions

Tiotropium combined with low-dose theophylline significantly improved the symptoms and general health of patients with stable COPD of groups B and D after 6 months of follow-up. Additionally, this therapy also improved the indicators of small airway function.

Trial Registration

Chinese Clinical Trial Registry (Registry ID: ChiCTR1800019027).

     

Relationship between gait kinematics and walking energy expenditure during pregnancy in South African women

Background

Various musculoskeletal changes occurring during pregnancy may lead to the change in gait and contribute to the increase in walking energy expenditure. Previous research indicates that changes in gait mechanics may lead to the increase in mechanical work required during walking. However, there is little information to indicate if changes in gait mechanics during pregnancy have impact on active or total energy expenditure. Therefore, the primary aim of this study was to investigate the relationship between changes in gait kinematics and walking energy expenditure in pregnant women.

Methods

Thirty-five women (mean age?=?27.5?±?6.1 years) volunteered for the study during various stages of pregnancy (1st trimester average?=?12.1?±?2.2 weeks; 2nd trimester?=?22.3?±?2.6 weeks; 3rd trimester?=?31.4?±?2.6 weeks). 3D motion analysis was used to assess changes in kinematic parameters during walking at self-selected pace. Resting metabolic rate, and walking energy expenditure expressed in terms of rate and cost of O₂ were analysed with portable metabolic analyser.

Results

Only medio-lateral deviation of centre of gravity (COG_ML) increased 13.6% between the 1st and 2nd, and 39.3% between 2nd and 3rd trimester (p?≤?0.001). However, self-selected walking speed depicted strong significant positive linear relationship with net O₂ rate (r?=?0.70; p?≤?0.001), and was strongly associated with the vertical excursion of the COG (r?=?0.75, p?≤?0.001).

Conclusions

Changes in gait mechanics during pregnancy may lead to an increase in walking energy expenditure. However, the consequent increase in walking energy cost may not be sufficient to offset the natural energy sparing mechanism.

     

Efficacy and Tolerability of Fixed-Dose Combination Perindopril/Indapamide in Hypertensive Patients with a History of Stroke or Transient Ischemic Attack: PICASSO Trial

Introduction

In everyday medical practice, physicians often need to manage patients whose blood pressure is not well controlled. Those with a history of cerebrovascular disease are a high-risk group in need of rapid blood pressure control.

Methods

The PICASSO study was a real-life, observational trial involving 9257 inadequately treated hypertensive patients who were switched from previous therapy to the fixed-dose combination of perindopril 10 mg/indapamide 2.5 mg (PI) for 3 months. A subanalysis of data of 1117 hypertensive patients who met the clinical criteria of previous stroke or transient ischemic attack was performed. Twenty-four hour ambulatory blood pressure measurements (ABPMs) were also done in a small group of patients (n:38).

Results

At baseline, mean systolic/diastolic blood pressure (SBP/DBP) was 161.5?±?15.2/93.1?±?9.9 mmHg. After 1 month with the fixed dose of PI, average office SBP/DBP decreased to 140.0?±?11.9/83.5?±?7.7 mmHg. After 3 months, SBP/DBP had dropped to 132.9?±?9.8/80.0?±?6.2 mmHg, by 28.6?±?15.5/13.1?±?10.0 mmHg (p?<?0.001). Blood pressure control rate (<?140/90 mmHg) was 67.3% after 3 months. When data were stratified by baseline blood pressure, decreases in SBP/DBP were statistically significant in patients with all grades (1–3) of hypertension. In patients previously treated with an angiotensin-converting enzyme inhibitor?±?hydrochlorothiazide (n?=?677), blood pressure decreased by 29.8?±?15.5/13.3?±?10.2 mmHg (p?<?0.001). Decreases in 24-h ABPM values were also significant (n?=?38). Treatment was well tolerated; only a few adverse events were recorded.

Conclusion

This study suggests that fixed combination perindopril 10 mg/indapamide 2.5 mg is an effective and well-tolerated treatment for patients with a history of stroke or transient ischemic attack.

Funding

EGIS Pharmaceuticals Plc.

     

Phase 1 Evaluation of [<Superscript>64</Superscript>Cu]DOTA-Patritumab to Assess Dosimetry,Apparent Receptor Occupancy,and Safety in Subjects with Advanced Solid Tumors

Purpose

The purpose of this study was to evaluate the safety, dosimetry, and apparent receptor occupancy (RO) of [⁶⁴Cu]DOTA-patritumab, a radiolabeled monoclonal antibody directed against HER3/ERBB3 in subjects with advanced solid tumors.

Procedures

Dosimetry subjects (n?=?5) received [⁶⁴Cu]DOTA-patritumab and underwent positron emission tomography (PET)/X-ray computed tomography (CT) at 3, 24, and 48 h. Evaluable RO subjects (n?=?3 out of 6) received [⁶⁴Cu]DOTA-patritumab at day 1 and day 8 (after 9.0 mg/kg patritumab) followed by PET/CT at 24 h post-injection. Endpoints included safety, tumor uptake, and efficacy.

Results

The tumor SUV_max (±?SD) was 5.6?±?4.5, 3.3?±?1.7, and 3.0?±?1.1 at 3, 24, and 48 h in dosimetry subjects. The effective dose and critical organ dose (liver) averaged 0.044?±?0.008 mSv/MBq and 0.46?±?0.086 mGy/MBq, respectively. In RO subjects, tumor-to-blood ratio decreased from 1.00?±?0.32 at baseline to 0.57?±?0.17 after stable patritumab, corresponding to a RO of 42.1?±?3.

Conclusions

[⁶⁴Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.

     

Acceleration of the learning curve for mastering basic critical care echocardiography using computerized simulation

Purpose

To assess the impact of computerized transthoracic echocardiography (TTE) simulation on the learning curve to achieve competency in basic critical care echocardiography (CCE).

Methods

In this prospective bicenter study, noncardiologist residents novice in ultrasound followed either a previously validated training program with adjunctive computerized simulation on a mannequin (two 3 h-sessions; Vimedix simulator, CAE Healthcare) (interventional group; n?=?12) or solely the same training program (control group; n?=?12). All trainees from the same institution were assigned to the same study group to avoid confusion bias. Each trainee was evaluated after 1 (M1), 3 (M3) and 6 (M6) months of training using our previously validated scoring system. Competency was defined by a score?≥?90% of the maximal value.

Results

The 24 trainees performed 965 TTE in patients with cardiopulmonary compromise during their 6-month rotation. Skills assessments relied on 156 TTE performed in 106 patients (mean age 53?±?14 years; mean Simplified Acute Physiologic Score 2: 55?±?19; 79% ventilated). When compared to the control group, trainees of the interventional group obtained a significantly higher mean skills assessment score at M1 (41.5?±?4.9 vs. 32.3?±?3.7: P?=?0.0004) and M3 (45.8?±?2.8 vs. 42.3?±?3.7: P?=?0.0223), but not at M6 (49.7?±?1.2 vs. 50.0?±?2.7: P?=?0.6410), due to higher practical and technical skills scores. Trainees of the control group required significantly more supervised TTE to obtain competency than their counterparts (36?±?7 vs. 30?±?9: p?=?0.0145).

Conclusions

Adjunctive computerized simulation accelerates the learning curve of basic CCE in improving practical and technical skills and reduces the number of TTE examinations required to reach competency.

     

Baseline [<Superscript>18</Superscript>F]FMISO μPET as a Predictive Biomarker for Response to HIF-1α Inhibition Combined with 5-FU Chemotherapy in a Human Colorectal Cancer Xenograft Model

Purpose

The purpose of this study was to characterize imaging biomarkers for the potential benefit of hypoxia-inducible factor-1 (HIF-1)α inhibition (by PX-12) during 5-fluorouracil (5-FU) chemotherapy in the treatment of colorectal cancer (CRC).

Procedures

Therapy response to 5-FU?±?PX-12 was assessed with baseline [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO) and longitudinal 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) positron emission computed tomography (μPET/CT) in CRC xenograft model (n?=?36) during breathing of a hypoxic (10 % O₂) or normoxic (21 % O₂) atmosphere. Ex vivo, immunohistochemistry was performed.

Results

Baseline [¹⁸F]FMISO uptake and relative tumor volume (RTV) 2 days after 5-FU or 5-FU?+?PX-12 administration correlated significantly (p?≤?0.01). Under hypoxic breathing conditions, [¹⁸F]FDG uptake (?53.1?±?8.4 %) and Ki67 expression (?16 %) decreased and RTV stagnated in the 5-FU?+?PX-12 treatment group, but not in 5-FU alone-treated tumors. Under normoxic breathing, [¹⁸F]FDG uptake (?23.5?±?15.2 % and ?72.8?±?7.1 %) and Ki67 expression (?5 % and ?19 %) decreased and RTV stagnated in both the 5-FU and the combination treatment group, respectively.

Conclusion

Baseline [¹⁸F]FMISO μPET may predict the beneficial effect of HIF-1α inhibition during 5-FU chemotherapy in CRC.

     

Concurrent validity of the Gyko inertial sensor system for the assessment of vertical jump height in female sub-elite youth soccer players

Background

The aim of the present study was to verify concurrent validity of the Gyko inertial sensor system for the assessment of vertical jump height.

Methods

Nineteen female sub-elite youth soccer players (mean age: 14.7?±?0.6 years) performed three trials of countermovement (CMJ) and squat jumps (SJ), respectively. Maximal vertical jump height was simultaneously quantified with the Gyko system, a Kistler force-plate (i.e., gold standard), and another criterion device that is frequently used in the field, the Optojump system.

Results

Compared to the force-plate, the Gyko system determined significant systematic bias for mean CMJ (?0.66 cm, p?<?0.01, d?=?1.41) and mean SJ (?0.91 cm, p?<?0.01, d?=?1.69) height. Random bias was?±?3.2 cm for CMJ and?±?4.0 cm for SJ height and intraclass correlation coefficients (ICCs) were “excellent” (ICC?=?0.87 for CMJ and 0.81 for SJ). Compared to the Optojump device, the Gyko system detected a significant systematic bias for mean CMJ (0.55 cm, p?<?0.05, d?=?0.94) but not for mean SJ (0.39 cm) height. Random bias was?±?3.3 cm for CMJ and?±?4.2 cm for SJ height and ICC values were “excellent” (ICC?=?0.86 for CMJ and 0.82 for SJ).

Conclusion

Consequently, apparatus specific regression equations were provided to estimate true vertical jump height for the Kistler force-plate and the Optojump device from Gyko-derived data. Our findings indicate that the Gyko system cannot be used interchangeably with a Kistler force-plate and the Optojump device in trained individuals. It is suggested that practitioners apply the correction equations to estimate vertical jump height for the force-plate and the Optojump system from Gyko-derived data.

     

Left ventricular synchrony,torsion, and recoil mechanics in Ebstein’s anomaly: insights from cardiovascular magnetic resonance

Background

Disease progression and heart failure development in Ebstein’s Anomaly (EA) of the tricuspid valve is characterized by both right and left ventricular (LV) deterioration. The mechanisms underlying LV dysfunction and their role in heart failure development are incompletely understood. We hypothesized that LV dyssynchrony and impaired torsion and recoil mechanics induced by paradoxical movement of the basal septum may play a role in heart failure development.

Methods

31 EA patients and 31 matched controls underwent prospective cardiovascular magnetic resonance (CMR). CMR feature tracking (CMR-FT) was performed on apical, midventricular and basal short-axis and 4D–volume analysis was performed using three long-axis views and a short axis cine stack employing dedicated software. Circumferential uniformity ratio estimates (CURE) time-to-peak-based circumferential systolic dyssynchrony index (C-SDI), 4D volume analysis derived SDI (4D–SDI), torsion (Tor) and systolic (sysTR) and diastolic torsion rate (diasTR) were calculated for the LV. QRS duration, brain natriuretic peptide, NYHA and Total R/L-Volume Index (R/L Index) were obtained.

Results

EA patients (31.5 years; controls 31.4 years) had significantly longer QRS duration (123.35 ms?±?26.36 vs. 97.33 ms ±?11.89 p <?0.01) and showed more LV dyssynchrony (4D–SDI 7.60%?±?4.58 vs. 2.54%?±?0.62, p <?0.001; CURE 0.77?±?0.05 vs. 0.86?±?0.03, p?<?0.001; C-SDI 7.70?±?3.38 vs. 3.80?±?0.91, p =?0.001). There were significant associations of LV dyssynchrony with heart failure parameters and QRS duration. Although torsion and recoil mechanics did not differ significantly (p >?0.05) there was an association of torsion and recoil mechanics with dyssynchrony parameters CURE (sysTR r =??0.426; p =?0.017, diasTR r =?0.419; p =?0.019), 4D–SDI (sysTR r =?0.383; p =?0.044) and C-SDI (diasTR r =??0.364; p?=?0.044).

Conclusions

EA is characterized by LV intra-ventricular dyssynchrony, which is associated with heart failure and disease severity parameters. Markers of dyssynchrony can easily be quantified from CMR-FT, and may have a role in the assessment of altered cardiac function, carrying potential management implications for EA patients.

     

Clinical Benefits Over Time Associated with Use of V-Go Wearable Insulin Delivery Device in Adult Patients with Diabetes: A Retrospective Analysis

Introduction

Advances in insulin delivery have improved outcomes in patients with diabetes. This study evaluated the impact of V-Go^® Wearable Insulin Delivery device on glycated hemoglobin (A1C) and insulin total daily dose (TDD) in patients with diabetes not achieving glycemic targets.

Methods

Electronic medical record data was obtained for adult patients with A1C?>?7% treated at a multicenter endocrine practice who initiated V-Go between August 2012 and August 2015. Data were collected at baseline and for up to four follow-up visits, and were analyzed overall, stratified by insulin use at baseline, and for patients prescribed a basal-bolus insulin regimen delivered by multiple daily injections (MDI) at baseline. Economic evaluations were conducted in patients previously prescribed MDI regimens.

Results

Patients (N?=?103) were evaluated after a mean of 2, 6, 10, and 14 months of V-Go use. Baseline glycemic control was poor (A1C?>?9%) in 59% of patients. Significant, sustained reductions in A1C compared with baseline were observed at every visit (p?<?0.0001), with mean?±?SE decrease of 1.67?±?0.24% after 14 months. For patients prescribed insulin at baseline (n?=?80), TDD was significantly reduced at all visits (p?<?0.0001), with mean?±?SE reduction of 17?±?4.5 units/day at 14 months. Patients previously prescribed MDI therapy (n?=?58) benefited from 1.53?±?0.31% (p?<?0.001) A1C reduction and TDD decrease of 30?±?5 units/day after 14 months. Direct pharmacy wholesale acquisition costs for diabetes therapeutics were reduced by $25.00/patient/month.

Conclusion

Use of V-Go was associated with improved glycemic control and decreased TDD. For patients previously prescribed basal-bolus MDI therapy, switching to insulin therapy with V-Go resulted in pharmacy cost savings based on wholesale acquisition costs. V-Go offers an efficacious method of insulin delivery that improves outcomes in patients and can reduce costs.

Funding

Valeritas, Inc.

     

Reliability and concurrent validity of the International Physical Activity Questionnaire short form among pregnant women

Background

The International Physical Activity Questionnaire short-form (IPAQ-SF) is frequently used to assess physical activity (PA) level in the general adult population including pregnant women. However, the reliability and validity of the questionnaire in pregnancy is unknown. Therefore, the aims of the present study were to investigate test-retest reliability and concurrent validity of IPAQ-SF among pregnant women, and whether PA is reported differently among those who fulfill (active) vs. do not fulfill (inactive) recommendations of ≥150 min of weekly moderate intensity PA in pregnancy.

Method

Test-retest reliability was examined by answering IPAQ-SF twice, two weeks apart (n?=?88). To assess validity, IPAQ-SF was compared to the physical activity monitor SenseWear Armband® (SWA) (n?=?64). The participants wore SWA for 8 consecutive days before answering IPAQ-SF. PA level was reported as time spent in moderate-, vigorous- and moderate-to-vigorous intensity PA (MPA, VPA and MVPA) corresponding to the cut-off points 3–6, >6 and >3 Metabolic Equivalents (METs), respectively.

Results

Test-retest intraclass-correlation of MPA, VPA and MVPA ranged from 0.81-0.84 (95% Confidence Intervals: 0.69,0.90). Comparing time spent performing PA at various intensities; the mean differences and limits of agreement (±1.96 Standard Deviation) from Bland-Altman plots were?84?±?402 min/week for MPA,?85?±?452 min/week for MVPA and 26?±?78 min/week for VPA, illustrating that the total group under-reported MPA by 72% and MVPA by 52%, while VPA was over-reported by 1400%. For the inactive group corresponding numbers were 44?±?327 min/week for MPA, 52?±?355 min/week for MVPA and 16?±?33 min/week for VPA, illustrating that the inactive group over-reported MPA by 13% and MVPA by 49%, while VPA was not detected by SWA, but participants reported 16 min of VPA/week. In contrast, corresponding numbers for the active group were?197?±?326 min/week for MPA,?205?±?396 min/week for MVPA and 35?±?85 min/week for VPA, illustrating that the active group under-reported MPA by 81% and MVPA by 60%, while they over-reported VPA by 975%.

Conclusion

IPAQ-SF had good test-retest reliability, but low to fair concurrent validity for MPA, VPA and MVPA compared to an objective criterion measure among pregnant women. Further, women fulfilling PA guidelines in pregnancy under-reported, while inactive women over-reported PA level.

     

Procalcitonin algorithm to guide initial antibiotic therapy in acute exacerbations of COPD admitted to the ICU: a randomized multicenter study

Purpose

To compare the efficacy of an antibiotic protocol guided by serum procalcitonin (PCT) with that of standard antibiotic therapy in severe acute exacerbations of COPD (AECOPDs) admitted to the intensive care unit (ICU).

Methods

We conducted a multicenter, randomized trial in France. Patients experiencing severe AECOPDs were assigned to groups whose antibiotic therapy was guided by (1) a 5-day PCT algorithm with predefined cutoff values for the initiation or stoppage of antibiotics (PCT group) or (2) standard guidelines (control group). The primary endpoint was 3-month mortality. The predefined noninferiority margin was 12%.

Results

A total of 302 patients were randomized into the PCT (n?=?151) and control (n?=?151) groups. Thirty patients (20%) in the PCT group and 21 patients (14%) in the control group died within 3 months of admission (adjusted difference, 6.6%; 90% CI ??0.3 to 13.5%). Among patients without antibiotic therapy at baseline (n?=?119), the use of PCT significantly increased 3-month mortality [19/61 (31%) vs. 7/58 (12%), p?=?0.015]. The in-ICU and in-hospital antibiotic exposure durations, were similar between the PCT and control group (5.2?±?6.5 days in the PCT group vs. 5.4?±?4.4 days in the control group, p?=?0.85 and 7.9?±?8 days in the PCT group vs. 7.7?±?5.7 days in the control group, p?=?0.75, respectively).

Conclusion

The PCT group failed to demonstrate non-inferiority with respect to 3-month mortality and failed to reduce in-ICU and in-hospital antibiotic exposure in AECOPDs admitted to the ICU.

     

Effects of heat stress and dehydration on cognitive function in elite female field hockey players

Background

It has previously been suggested that heat exposure and hypohydration have negative effects on cognitive performance, which may impact upon sporting performance. The aim of the present study was to examine the independent effects of heat stress and hypohydration on cognitive performance in elite female field hockey players.

Methods

Eight unacclimatised elite field hockey players (age: 22?±?3 y; height: 1.68?±?0.05 m; body mass: 63.1?±?6.0 kg) completed a cognitive test battery before and after 50 min of field hockey specific exercise on a treadmill in four experimental trials; two in hot conditions (33.3?±?0.1 °C), and two in moderate (16.0?±?3.0 °C), both with and without ad libitum water intake.

Results

On the visual search test, participants were faster overall in the heat (1941 vs. 2104 ms, p?=?0.001). Response times were quicker in the heat on the Sternberg paradigm (463 vs. 473 ms, p?=?0.024) and accuracy was improved (by 1.9%, p?=?0.004). There was no effect of hydration status on any of the markers of cognitive function.

Conclusions

Overall, the findings suggest that in elite field hockey players exposure to heat enhances response times and/or accuracy on a battery of cognitive function tests. However, hypohydration does not appear to affect cognitive performance in elite field hockey players.

     

Lack of agreement between thermodilution and electrical velocimetry cardiac output measurements

Objective

The modified algorithm for the non-invasive determination of cardiac output (CO) by electrical bioimpedance—electrical velocimetry (EV^®)—has been reported to give reliable results in comparison with echocardiography and pulmonary arterial thermodilution (PA-TD) in patients either before or after cardiac surgery. The present study was designed to determine whether EV^®-CO measurements reflect intraindividual changes in CO during cardiac surgery.

Design

Prospective, observational study.

Setting

Operating room (OR) and intensive care unit (ICU) of a university hospital.

Patients

Twenty-nine patients undergoing elective cardiac surgery.

Interventions

None.

Measurements

CO was determined simultaneously by PA-TD and EV^® after induction of anesthesia (t1) and 4.9?±?3.5?h after ICU admission (t2).

Results

TD-CO was 3.9?±?1.4 and 5.4?±?1.1 l/min at t1 and t2 (?p?®-CO was 4.3?±?1.1 and 4.9?±?1.5 l/min at t1 and t2 (?p?=?0.013). Bland–Altman analysis showed a bias of ?0.4 l/min and 0.4 l/min and a precision of 3.2 and 3.6 l/min (34.3% and 67.4%) at t1 and t2, respectively. Analysis of the individual pre- to postoperative changes in CO with both methods revealed bidirectional changes in n?=?12 patients and unidirectional changes with a difference greater than 50% and less than 50% in n?=?9 and n?=?8 patients, respectively.

Conclusions

The disagreement between PA-TD and EV^®-CO measurements after anesthesia induction and after ICU admission, as well as the fact that thoracic bioimpedance did not adequately reflect pre- to postoperative changes in CO, questions the reliability of EV^®-CO measurements in cardiac surgery patients and contrasts sharply with previous studies.

     

Differences between first-generation and second-generation drug-eluting stent regarding in-stent neoatherosclerosis characteristics: an optical coherence tomography analysis

We compared first-generation and second-generation drug-eluting stent (DES) with respect to neoatherosclerosis using optical coherence tomography or optical frequency domain imaging. In-stent restenoses in 102 first-generation and 114 second-generation DES were retrospectively assessed. Neoatherosclerosis, which was defined as the presence of lipid-laden neointima or calcification inside a stent, was observed in 33 (27.2%) and 31 (32.4%) lesions in the first-generation and second-generation DES respectively. In the first-generation DES group, the lipid length was significantly longer (5.5?±?3.8 vs. 3.1?±?2.1 mm, P?=?0.0007), the lipid arc was significantly larger (324?±?70° vs. 250?±?94°, P?=?0.002), the prevalence of a 360° lipid arc was significantly greater (58 vs. 31%, P?=?0.03), and the fibrous cap was significantly thinner (153?±?85 vs. 211?±?95 µm, P?=?0.02) compared with those in the second-generation DES group. These differences remained significant after adjusting for the age of the stent (lipid length: P?<?0.001; lipid arc: P?=?0.019; and fibrous cap thickness: P?<?0.001). The proliferation course and stability of neoatherosclerosis over time might be superior in second-generation DES.