Interventions in the diagnosis and adoption of pacemaker therapy in sinus node dysfunction patients: Results from the IMPROVE Brady study.

AIMS: IMPROVE Brady assessed whether a process improvement intervention could increase adoption of guideline-based therapy in sinus node dysfunction (SND) patients. METHODS: /Results: IMPROVE Brady was a sequential, prospective, quality improvement initiative conducted in India and Bangladesh. Patients with symptomatic bradycardia were enrolled. In Phase I, physicians assessed and treated patients per standard care. Phase II began after implementing educational materials for physicians and patients. Primary objectives were to evaluate the impact of the intervention on SND diagnosis and pacemaker (PPM) implant. SF-12 quality of life (QoL) and Zarit burden surveys were collected pre- and post-PPM implant. A total of 978 patients were enrolled (57.7 ± 14.8 years, 75% male), 508 in Phase I and 470 in Phase II. The diagnosis of SND and implantation of PPM increased significantly from Phase I to Phase II (72% vs. 87%, P < 0.001 and 17% vs. 32%, P < 0.001, respectively). Pacemaker implantation was not feasible in 41% of patients due to insurance/cost barriers which was unaltered by the intervention. Both patient QoL and caregiver burden improved at 6-months post-PPM implant (P < 0.001). CONCLUSIONS: A process improvement initiative conducted at centers across India and Bangladesh significantly increased the diagnosis of SND and subsequent treatment with PPM therapy despite the socio-economic constraints.

Identifying high risk patients post myocardial infarction with reduced left ventricular function using loop recorders INSPIRE-ELR clinical study.

AIMS: Sudden cardiac death (SCD) continues to be a devastating complication amongst survivors of myocardial infarction (MI). Mortality is high in the initial months after MI. The aims of the INSPIRE-ELR study were to assess the proportion of patients with significant arrhythmias early after MI and the association with mortality during 12 months of follow-up. METHODS: The study included 249 patients within 14 days after MI with left ventricular ejection fraction (LVEF) ≤35% at discharge in 11 hospitals in India. Patients received a wearable external loop recorder (ELR) 5 ± 3 days after MI to monitor arrhythmias for 7 days. RESULTS: Patients were predominantly male (86%) with a mean age of 56 ± 12 years. In 82%, reperfusion had been done and all received standard of care cardiovascular medications at discharge. LVEF was 32.2 ± 3.9%, measured 5.1 ± 3.0 days after MI. Of the 233 patients who completed monitoring (7.1 ± 1.5 days), 81 (35%) experienced significant arrhythmias, including Ventricular Tachycardia/Fibrillation (VT/VF): 10 (4.3%); frequent Premature Ventricular Contractions (PVCs): 65 (28%); Atrial Fibrillation (AF): 8 (3.4%); chronic atrial flutter: 4 (1.7%); 2nd or 3rd degree Atrioventricular (AV) block: 4 (1.7%); and symptomatic bradycardia: 8 (3.4%). In total, 26 patients died. Mortality was higher in patients with clinically significant arrhythmia (at 12 months: 23.6% vs 4.8% with 19 vs 7 deaths, hazard ratio (HR) = 5.5, 95% confidence interval (CI) 2.3 to 13.0, p < 0.0001). Excluding 7 deaths during ELR monitoring, HR = 4.5, p < 0.001. CONCLUSION: ELR applied in patients with acute MI and LV dysfunction at the time of discharge identifies patients with high mortality risk.

Cardiac resynchronization therapy is associated with improvement in clinical outcomes in Indian heart failure patients: Results of a large, long-term observational study.

BACKGROUND: Heart failure (HF) is a common health problem in South Asia, and its incidence and prevalence are projected to rise. Cardiac resynchronization therapy (CRT) has been shown to improve mortality, reduce hospitalizations, and improve symptoms in selected patients with HF. The South Asian Systolic Heart Failure Registry (SASHFR) was designed to be a large and comprehensive registry of Indian HF patients with the purpose of enhancing the quality of care and clinical outcomes of HF patients by promoting the adoption of evidence-based, guideline-recommended therapies, in particular CRT. METHODS: Overall, 471 patients on optimized medical therapy and meeting CRT implantation guidelines were followed up in 12 Indian hospitals. During the 2-year follow-up period, clinical response in terms of clinical composite score, overall performance and changes in HF performance metrics, mortality and hospitalizations rates were evaluated. RESULTS: Of 471 patients, 116 (24.6%) accepted to be implanted with a CRT device, while 355 (75.4%) refused, financial constraints being the main reason for refusing a CRT device. The study met its primary outcome, as the number of patients associated with an improvement in clinical composite score at 24 months was significantly higher (69.1%) in the CRT group than in the no-CRT group (44.7%) [odds ratio = 2 (95% confidence interval 1.25-3.20), p = 0.004]. Also, changes in HF metrics, mortality and hospitalizations rates indicated a more favorable response among patients who underwent CRT. CONCLUSIONS: The results from the SASHFR registry show a clear superiority of CRT over optimal pharmacological therapy in terms of improvement in clinical conditions among HF patients. The low rate of CRT acceptance, in patients indicated to this therapy, highlights the need for new health-care policies to improve awareness about HF disease and its therapies and possibly to enhance financial coverage of indicated therapies.

Software-controlled, highly automated intrafraction prostate motion correction with intrafraction stereographic targeting: System description and clinical results.

PURPOSE: A new system for software-controlled, highly automated correction of intrafraction prostate motion," intrafraction stereographic targeting" (iSGT), is described and evaluated. METHODS: At our institute, daily prostate positioning is routinely performed at the start of treatment beam using stereographic targeting (SGT). iSGT was implemented by extension of the SGT software to facilitate fast and accurate intrafraction motion corrections with minimal user interaction. iSGT entails megavoltage (MV) image acquisitions with the first segment of selected IMRT beams, automatic registration of implanted markers, followed by remote couch repositioning to correct for intrafraction motion above a predefined threshold, prior to delivery of the remaining segments. For a group of 120 patients, iSGT with corrections for two nearly lateral beams was evaluated in terms of workload and impact on effective intrafraction displacements in the sagittal plane. RESULTS: SDs of systematic (Σ) and random (σ) displacements relative to the planning CT measured directly after initial SGT setup correction were <0.5 and <0.8 mm, respectively. Without iSGT corrections, effective Σ and σ for the 11-min treatments would increase to Σ(eff) < 1.1 mm and σ(eff) < 1.2 mm. With the iSGT procedure with an action level of 4 mm, effective positioning errors were reduced to Σ(eff) < 0.8 mm and σ(eff) < 1.0 mm, with 23.1% of all fractions requiring a correction. Computer simulations demonstrated that with an action level of 2 mm, the errors would have been reduced to Σ(eff) < 0.6 mm and σ(eff) < 0.7 mm, requiring corrections in 82.4% of the fractions. Because iSGT is highly automated, the extra time added by iSGT is <30 s if a correction is required. CONCLUSIONS: Without increasing imaging dose, iSGT successfully reduces intrafraction prostate motion with minimal workload and increase in fraction time. An action level of 2 mm is recommended.

Day-to-day reproducibility of prostate intrafraction motion assessed by multiple kV and MV imaging of implanted markers during treatment.

PURPOSE: When one is performing online setup correction for prostate positioning displacements prior to daily dose delivery, intrafraction motion can become a limiting factor to prostate targeting accuracy. The aim of this study was to quantify and characterize prostate intrafraction motion assessed by multiple kilovoltage (kV) and megavoltage (MV) imaging of implanted markers during treatment in a large patient group. METHODS AND MATERIALS: Intrafraction motion in the sagittal plane was studied by retrospective analysis of displacements of implanted gold markers on (nearly) lateral kV and MV images obtained at various time points during the treatment fractions (mean, 27 per patient) in 108 consecutive patients. The effective prostate motion in a fraction was defined as the time-weighted mean displacement. RESULTS: Prostate displacements in the sagittal plane increased during the fraction (mean, 0.2 ± 0.2 mm/min). Forty percent of patients had a systematic (i.e., appearing in all fractions) effective displacement in the sagittal plane greater than 2 mm. Observed effective population mean-of-means (µeff) +/- systematic (Σeff) intrafraction motion (µ(eff) ± Σ(eff)) was 0.9 ± 1.1 mm and 0.6 ± 1.0 mm for the anterior-posterior and superior inferior directions, respectively. Corresponding random motion (σ(eff)) was 1.2 mm and 1.1 mm. Mean effective prostate motion in the first 5 fractions was predictive for mean effective displacement in the remaining fractions (p < 0.001). CONCLUSION: For a large subgroup of patients, the systematic component of intrafraction prostate motion was substantial. Intrafraction motion correction prior to each beam delivery or offline corrections could likely be beneficial for the subgroup of patients with significant motion. The systematic component is well predicted by measurements in the initial fractions.

In vivo optical path lengths and path length resolved doppler shifts of multiply scattered light.

BACKGROUND AND OBJECTIVES: In laser Doppler measurements, perfusion values averaged over different and basically unknown path lengths are recorded. To facilitate quantitative path length resolved perfusion measurements, we developed a phase modulated Mach-Zehnder interferometer with spatially separated fibers for illumination and detection. The goal of this study is to measure in vivo optical path lengths and path length resolved Doppler shifts and to compare these with conventional laser Doppler perfusion measurements. STUDY DESIGN/MATERIALS AND METHODS: With a phase modulated Mach-Zehnder interferometer, we performed path length resolved perfusion measurements on human skin and its variations to external stimuli and compared these with conventional laser Doppler perfusion measurements. The method was evaluated in three human subjects on the dorsal side of the forearm to establish inter-individual within-site variations. Measurements were performed at three different locations of one individual for observing intra-individual inter-site variations resulting from the heterogeneity of the tissue, both in the static matrix and in the microvascular architecture of the skin. In all measurements, perfusion was simultaneously measured with a conventional laser Doppler perfusion monitor. RESULTS: In this study, we show the first results of path length resolved perfusion measurements in skin and its variations to occlusion and Capsicum cream provocation. From our data, we deduced the Doppler shifted fraction of photons, which is related to the blood volume, and the path length dependent average Doppler shift, which is related to the mean velocities of red blood cells. The Doppler shifted fraction of photons is decreased from 28% to 18% during occlusion and increases to 41% when capsicum cream was applied to the skin. Inter- and intra-individual inter-site measurements demonstrated variations in optical path length distributions and path length resolved Doppler shifts. The Doppler shifted fraction of photons measured on the fingertip is about 38% and that measured on the dorsal and palmar sides of the forearm are 32% and 17%, respectively. The path length distributions depend on the skin site that is being probed and the intra-individual inter-site variability is higher than the inter-individual within-site variability measured on comparable sites between different individuals. CONCLUSIONS: In this study, we demonstrated, for the first time to our knowledge, that in vivo path length resolved perfusion measurements are feasible. Optical path length distributions of multiply scattered light, spanning a range of 0-6 mm, and their response to external stimuli such as occlusion and capsicum cream provocation have been measured. This method will enable better interpretation of inter- and intra-individual inter-site variations in the LDF readings that are introduced by the variance in tissue optical properties. The inter- and intra-individual inter-site variations measured with our setup results indicate that that these variations should be taken into account while comparing the perfusion readings from comparable sites between individuals and from different sites of the same individual. Furthermore, the observed inter- and intra-individual inter-site variations in path length resolved Doppler measurements indicate the inherent limitation of conventional LDPM that restrict its clinical usefulness, due to its dependence on the unknown photon path length. Consequently, this method will enable to correctly interpret or counter-act the inter- and intra-individual inter-site variations in the LDF readings introduced by the variance in tissue optical properties. This approach also enables to discriminate between the Doppler-shifted photons resulting from interaction with the moving red blood cells and the non-shifted light scattered only by the surrounding static tissue matrices.

Measurement of particle flux in a static matrix with suppressed influence of optical properties, using low coherence interferometry.

Perfusion measurements using conventional laser Doppler techniques are affected by the variations in tissue optical properties. Differences in absorption and scattering will induce different path lengths and consequently will alter the probability that a Doppler shift will occur. In this study, the fraction of Doppler shifted photons and the Doppler broadening of a dynamic medium, are measured with a phase modulated low coherence Mach-Zehnder interferometer. Path length-resolved dynamic light scattering measurements are performed in various media having a constant concentration of dynamic particles inside a static matrix with different scattering properties and the results are compared with a conventional laser Doppler technique, with a simple model and with Monte Carlo simulations. We demonstrate that, for larger optical path lengths, the scattering coefficient of the static matrix in which the moving particles are embedded have a small to minimal effect on the measured fraction of Doppler shifted photons and on the measured average Doppler frequency of the Doppler shifted light. This approach has potential applications in measuring perfusion independent of the influence of optical properties in the static tissue matrix.

Review of methodological developments in laser Doppler flowmetry.

Laser Doppler flowmetry is a non-invasive method of measuring microcirculatory blood flow in tissue. In this review the technique is discussed in detail. The theoretical and experimental developments to improve the technique are reviewed. The limitations of the method are elaborated upon, and the research done so far to overcome these limitations is critically assessed.

Effect and safety of spinal cord stimulation for treatment of chronic pain caused by diabetic neuropathy.

AIM: Spinal cord stimulation (SCS) has been shown effective as a therapy for different chronic painful conditions, but the effectiveness of this treatment for pain as a result of peripheral diabetic neuropathy is not well established. The primary objectives of this study were to evaluate the effect and safety of SCS for treatment of pain and the effects on microcirculatory blood flow in the affected areas in patients with refractory peripheral diabetic neuropathy. METHOD: The study was designed as a prospective, open-label study. Data were collected during screening, at implant and at regular intervals, after initiation of therapy. Eleven diabetic patients with chronic pain in their lower limbs and no response to conventional treatment were studied. The SCS electrode was implanted in the thoracic epidural space. Neuropathic pain relief was assessed by Visual Analogue Scale (VAS) and microcirculatory skin perfusion was measured with Laser Doppler flowmetry. RESULTS: Nine subjects had significant pain relief with the percutaneous electrical stimulator. Average pain score for all nine patients was 77 at baseline and 34 at 6 months after implantation. At the end of the study, eight of nine patients continued to experience significant pain relief and have been able to significantly reduce their pain medication. For six of them, the stimulator was the sole treatment for their neuropathic pain. No significant changes in microcirculatory perfusion were recorded. CONCLUSION: Spinal cord stimulation offers an effective and safe therapy for chronic diabetic neuropathic pain.

Influence of tissue optical properties on laser Doppler perfusion imaging, accounting for photon penetration depth and the laser speckle phenomenon.

The influence of tissue optical properties on laser Doppler perfusion imaging (LDPI) is not well understood. We address this problem by quantifying the dependence of the signal response to tissue optical properties based on speckles or coherence areas and on photon statistics. We investigate the effect in vivo, showing the amplitude of photocurrent fluctuations in normal skin and port-wine stain with a range of beam diameters, and its relation to the speckle size variation difference between these two tissues. For the case of a low concentration of moving particles moving within a static turbid medium, a model is described and applied to predict the influence of speckles on the overall and depth sensitivity of LDPI, for a range of scattering levels and absorption levels. The results show that the speckle related effects on overall and depth sensitivity are large and that the depth sensitivity is highly likely to be misinterpreted without taking the speckle phenomenon into account.

The relationship between local scalp skin temperature and cutaneous perfusion during scalp cooling.

Cooling the scalp during administration of chemotherapy can prevent hair loss. It reduces both skin blood flow and hair follicle temperature, thus affecting drug supply and drug effect in the hair follicle. The extent to which these mechanisms contribute to the hair preservative effect of scalp cooling remains unknown. The purpose of this study was to establish a relationship between local scalp skin temperature and cutaneous blood flow during scalp cooling. We measured skin temperature and cutaneous perfusion during a cooling and re-warming experiment. Experiments on a single subject showed that the measurements were reproducible and that the response was identical for the two positions that were measured. Inter-subject variability was investigated on nine subjects. We found that for the first 10 degrees C of cooling, perfusion of the scalp skin decreases to below 40%. Perfusion can be further reduced to below 30% by a few degrees more cooling, but a plateau is reached after that. We found that a generally accepted relation in thermal physiology between temperature and perfusion (i.e. Q(10) relation) does not describe the data well, but we found an alternative relation that describes the average behavior significantly better.

Quantification of spatial intensity correlations and photodetector intensity fluctuations of coherent light reflected from turbid particle suspensions.

We present a model for predicting the spatial intensity correlation function of dynamic speckle patterns formed by light backscattered from turbid suspensions, and an experimental validation of these predictions. The spatial correlation varies remarkably with multiple scattering. The provided computational scheme is a step towards correctly interpreting signals obtained from instruments based on the measurement of dynamic speckle patterns in the far field.

Path-length-resolved measurements of multiple scattered photons in static and dynamic turbid media using phase-modulated low-coherence interferometry.

In optical Doppler measurements, the path length of the light is unknown. To facilitate quantitative measurements, we develop a phase-modulated Mach-Zehnder interferometer with separate fibers for illumination and detection. With this setup, path-length-resolved dynamic light scattering measurements of multiple scattered light in static and dynamic turbid media are performed. Optical path length distributions spanning a range from 0 to 11 mm are measured from the area under the phase modulation peak around the modulation frequency in the power spectrum. A Doppler-broadened phase modulation interference peak is observed that shows an increase in the average Doppler shift with optical path length, independent of absorption. Validation of the estimated path length distributions is done by measuring their deformation for increasing absorption and comparing these observations with predictions based on Lambert-Beer's law.

Evaluation of a multimode fiber optic low coherence interferometer for path length resolved Doppler measurements of diffuse light.

The performance of a graded index multimode fiber optic low coherence Mach-Zehnder interferometer with phase modulation is analyzed. Investigated aspects were its ability to measure path length distributions and to perform path length resolved Doppler measurements of multiple scattered photons in a turbid suspension of particles undergoing Brownian and translational motion. The path length resolution of this instrument is compared with a system using single mode fibers for illumination and detection. The optical path lengths are determined from the zero order moment of the phase modulation peak in the power spectrum. The weighted first moment, which is equal to the average Doppler shift, shows a linear response for different mean flow velocities within the physiological range.

Path-length-resolved optical Doppler perfusion monitoring.

We report the first path-length-resolved perfusion measurements on human skin measured with a phase-modulated low-coherence Mach-Zehnder interferometer with spatially separated fibers for illumination and detection. Optical path lengths of Doppler shifted and unshifted light and path-length-dependent Doppler broadening of multiply scattered light from skin are measured from the Doppler broadened interference peaks appearing in the power spectrum. Perfusion and its variations during occlusion are measured in real time for a given optical path length, and the results are compared with the perfusion signal obtained with a conventional laser Doppler perfusion monitor.