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.

     

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.

     

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).

     

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.

     

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.

     

Dynamic changes in injured myocardium,very early after acute myocardial infarction,quantified using T1 mapping cardiovascular magnetic resonance

Background

It has recently been suggested that myocardial oedema follows a bimodal pattern early post ST-segment elevation myocardial infarction (STEMI). Yet, water content, quantified using tissue desiccation, did not return to normal values unlike oedema quantified by cardiovascular magnetic resonance (CMR) imaging. We studied the temporal changes in the extent and intensity of injured myocardium using T1-mapping technique within the first week after STEMI.

Methods

A first group (n?=?31) underwent 3 acute 3?T CMR scans (time-point (TP) <?3?h, 24?h and 6?days), including cine, native shortened modified look-locker inversion recovery T1 mapping, T2* mapping and late gadolinium enhancement (LGE). A second group (n?=?17) had a single scan at 24?h with an additional T2-weighted sequence to assess the difference in the extent of area-at-risk (AAR) compared to T1-mapping.

Results

The mean T1 relaxation time value within the AAR of the first group was reduced after 24?h (P?<?0.001 for TP1 vs.TP2) and subsequently increased at 6?days (P?=?0.041 for TP2 vs.TP3). However, the extent of AAR quantified using T1-mapping did not follow the same course, and no change was detected between TP1&TP2 (P?=?1.0) but was between TP2 &TP3 (P?=?0.019). In the second group, the extent of AAR was significantly larger on T1-mapping compared to T2-weighted (42?±?15% vs. 39?±?15%, P?=?0.025). No change in LGE was detected while microvascular obstruction and intra-myocardial haemorrhage peaked at different time points within the first week of reperfusion.

Conclusion

The intensity of oedema post-STEMI followed a bimodal pattern; while the extent of AAR did not track the same course. This discrepancy has implications for use of CMR in this context and may explain the previously reported disagreement between oedema quantified by imaging and tissue desiccation.

     

Cardiovascular magnetic resonance left ventricular strain in end-stage renal disease patients after kidney transplantation

Background

Cardiovascular disease is a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD) and kidney transplant (KT) patients. Compared with left ventricular (LV) ejection fraction (LVEF), LV strain has emerged as an important marker of LV function as it is less load dependent. We sought to evaluate changes in LV strain using cardiovascular magnetic resonance imaging (CMR) in ESRD patients who received KT, to determine whether KT may improve LV function.

Methods

We conducted a prospective multi-centre longitudinal study of 79 ESRD patients (40 on dialysis, 39 underwent KT). CMR was performed at baseline and at 12?months after KT.

Results

Among 79 participants (mean age 55 years; 30% women), KT patients had significant improvement in global circumferential strain (GCS) (p?=?0.007) and global radial strain (GRS) (p?=?0.003), but a decline in global longitudinal strain (GLS) over 12?months (p?=?0.026), while no significant change in any LV strain was observed in the ongoing dialysis group. For KT patients, the improvement in LV strain paralleled improvement in LVEF (57.4?±?6.4% at baseline, 60.6%?±?6.9% at 12?months; p?=?0.001). For entire cohort, over 12?months, change in LVEF was significantly correlated with change in GCS (Spearman’s r?=???0.42, p?<?0.001), GRS (Spearman’s r?=?0.64, p?<?0.001), and GLS (Spearman’s r?=???0.34, p?=?0.002). Improvements in GCS and GRS over 12?months were significantly correlated with reductions in LV end-diastolic volume index and LV end-systolic volume index (all p?<?0.05), but not with change in blood pressure (all p?>?0.10).

Conclusions

Compared with continuation of dialysis, KT was associated with significant improvements in LV strain metrics of GCS and GRS after 12?months, which did not correlate with blood pressure change. This supports the notion that KT has favorable effects on LV function beyond volume and blood pessure control. Larger studies with longer follow-up are needed to confirm these findings.

     

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.

     

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.

     

Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80 Mg Once Daily in Stable Angina Patients in Real-World Practice

Introduction

Trimetazidine (TMZ) was shown to reduce angina symptoms and increase the exercise capacity in stable angina (SA) patients. A new formulation allowing a once-daily (od) dosage could improve patients’ satisfaction and adherence.

Methods

ODA was a 3-month, observational, multicenter, prospective Russian study in SA patients with persistent symptoms despite therapy. Angina attack frequency, short-acting nitrate (SAN) consumption, adherence to antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od were assessed in a real-world setting.

Results

A total of 3066 patients were included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to a significant (p?<?0.001) decrease in angina attack frequency (from 4.7?±?3.5 to 0.9?±?1.3/week) and SAN use (from 4.5?±?3.9 to 0.7?±?1.3/week). Overall tolerability and effectiveness were rated as “very good” by the majority of physicians. Medication adherence improved significantly, with good adherence reported by 56% of patients (vs. 24% at baseline, p?<?0.0001) and non-adherence by 3% (vs. 36% at baseline, p?<?0.0001) at month 3. Patient satisfaction with TMZ od was 9.5 [on a scale of 1 to 10 (very satisfied)]. Patients reported improved physical activity: more patients reported no limitations (15% vs. 1% at baseline p?<?0.01), slight limitation (46% vs. 5% at baseline, p?<?0.001) or moderate limitation (30% vs. 23%, p?<?0.01) and fewer patients reported substantial limitation (8% vs. 52% at baseline, p?<?0.001) or very marked reduction (1% vs. 19% at baseline, p?<?0.01) at month 3.

Conclusion

In this prospective, observational study, TMZ 80 mg od effectively reduced angina attacks and SAN consumption, improved physical activity and adherence and was well tolerated in chronic SA patients.

Trial Registration

ISRCTN registry Identifier, ISRCTN97780949.

Funding

Servier.

Plain Language Summary

Plain language summary available for this article.

     

Transthoracic echocardiography and mortality in sepsis: analysis of the MIMIC-III database

Purpose

While the use of transthoracic echocardiography (TTE) in the ICU is rapidly expanding, the contribution of TTE to altering patient outcomes among ICU patients with sepsis has not been examined. This study was designed to examine the association of TTE with 28-day mortality specifically in that population.

Methods and results

The MIMIC-III database was employed to identify patients with sepsis who had and had not received TTE. The statistical approaches utilized included multivariate regression, propensity score analysis, doubly robust estimation, the gradient boosted model, and an inverse probability-weighting model to ensure the robustness of our findings. Significant benefit in terms of 28-day mortality was observed among the TTE patients compared to the control (no TTE) group (odds ratio?=?0.78, 95% CI 0.68–0.90, p?<?0.001). The amount of fluid administered (2.5 vs. 2.1 L on day 1, p?<?0.001), use of dobutamine (2% vs. 1%, p?=?0.007), and the maximum dose of norepinephrine (1.4 vs. 1 mg/min, p?=?0.001) were significantly higher for the TTE patients. Importantly, the TTE patients were weaned off vasopressors more quickly than those in the no TTE group (vasopressor-free days on day 28 of 21 vs. 19, p?=?0.004).

Conclusion

In a general population of critically ill patients with sepsis, use of TTE is associated with an improvement in 28-day mortality.

     

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.

     

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.

     

ACTH and cortisol responses to CRH in acute,subacute, and prolonged critical illness: a randomized,double-blind,placebo-controlled,crossover cohort study

Purpose

Low plasma ACTH in critically ill patients may be explained by shock/inflammation-induced hypothalamus-pituitary damage or by feedback inhibition exerted by elevated plasma free cortisol. One can expect augmented/prolonged ACTH-responses to CRH injection with hypothalamic damage, immediately suppressed responses with pituitary damage, and delayed decreased responses in prolonged critical illness with feedback inhibition.

Methods

This randomized, double-blind, placebo-controlled crossover cohort study, compared ACTH responses to 100 µg IV CRH and placebo in 3 cohorts of 40 matched patients in the acute (ICU-day 3–6), subacute (ICU-day 7–16) or prolonged phase (ICU-day 17–28) of critical illness, with 20 demographically matched healthy subjects. CRH or placebo was injected in random order on two consecutive days. Blood was sampled repeatedly over 135 min and AUC responses to placebo were subtracted from those to CRH.

Results

Patients had normal mean?±?SEM plasma ACTH concentrations (25.5?±?1.6 versus 24.8?±?3.6 pg/ml in healthy subjects, P?=?0.54) but elevated free cortisol concentrations (3.11?±?0.27 versus 0.58?±?0.05 µg/dl in healthy subjects, P?<?0.0001). The order of the CRH/placebo injections did not affect the ACTH responses, hence results were pooled. Patients in the acute phase of illness had normal mean?±?SEM ACTH responses (5149?±?848 pg/mL min versus 4120?±?688 pg/mL min in healthy subjects; P?=?0.77), whereas those in the subacute (2333?±?387 pg/mL min, P?=?0.01) and prolonged phases (2441?±?685 pg/mL min, P?=?0.001) were low, irrespective of sepsis/septic shock or risk of death.

Conclusions

Suppressed ACTH responses to CRH in the more prolonged phases, but not acute phase, of critical illness are compatible with feedback inhibition exerted by elevated free cortisol, rather than by cellular damage to hypothalamus and/or pituitary.

     

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.

     

„Foam rolling“ und Wirbelsäulenbeweglichkeit – eine randomisierte kontrollierte Pilotstudie

Background

Despite limited evidence and little knowledge about underlying mechanisms or even potential risks, foam rolling (FR) has become a widely used tool for fitness and health purposes. Improvements in lower limb flexibility have been described, but there is a paucity of information for the spine.

Purpose

This pilot study aimed to investigate the effects of FR on trunk and spinal flexion and axial rotation in healthy subjects.

Methods

Spinal flexibility at maximal trunk flexion (sit and reach test) and maximal vertebral axial rotation (segments L1 and T4, dynamic video rasterstereography) was assessed in a randomized controlled repeated measures design (experimental and waiting control conditions separated by 1 week) before and after FR or a respective waiting time (control) in a sample of 19 active healthy females (age 26.1?±?3.6 years, body mass index 22.3?±?2.6?kg/m²). FR consisted of 2 repetitions (each 3?min with 60?s rest) for the paraspinal and lateral back muscles (10 roll cyles/min, average pressure approximately two thirds of body weight).

Results

We found a significant 2?cm increase in the sit and reach test results (p?<?0.001), which was, however, independent of the FR treatment (p?=?0.910). Vertebral rotation (L1, T4) did not change significantly (p?=?0.290–0.941). Although we observed 2?degree increases on average for the FR condition only, the time?×?treatment interactions did not indicate an FR effect (p?=?0.261–0.368).

Conclusion

Commonly accepted evidence for increases in lower limb flexibility after FR cannot be confirmed for spinal mobility after a single treatment in healthy active young women. The technical approach using dynamic rasterstereography to quantify axial spinal rotation appears to be promising for future FR investigations targeting patients with back complaints, provided methodical adaptations are taken into account.

     

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.

     

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.

     

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.