Biomedical subjects

Mathew Williams

Publications and source records attributed to Mathew Williams.

15 recordsLinked to original sources

PubMed2006

External validity of randomized controlled trials in COPD.

BACKGROUND: COPD is a heterogeneous disease comprising a wide range of clinical phenotypes, depending on the degree to which emphysema, chronic bronchitis, reversible bronchospasm and small airways inflammation are present. Not all of these phenotypes may be represented among the subjects included in randomized controlled drug trials (RCTs) in COPD, making it difficult for doctors to know to what extent RCT evidence applies to individual patients. From a respiratory health survey of adults randomly selected from the community, we have estimated the proportion of subjects with COPD who would have been eligible for inclusion in major COPD RCTs. METHODS: A postal survey was sent to 3500 randomly selected individuals aged 25-75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function tests. Subjects with COPD defined by post-bronchodilator spirometry were assessed against the eligibility criteria of 18 major RCTs cited in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. FINDINGS: Of 749 subjects completing the full survey, 117 had COPD. Of these, a median of 5% (range 0-20%) of subjects met inclusion criteria for the major RCTs. Of 55 subjects with COPD receiving treatment, 0-9% (median 5%) met inclusion criteria for the major RCTs. INTERPRETATION: The major COPD RCTs on which the GOLD treatment guidelines are based may have limited external validity. Over 90% of the COPD subjects in the community who were taking medication, did so on the basis of RCTs for which they would not have been eligible.

Adult↗

PubMed2006

External validity of randomised controlled trials in asthma: to whom do the results of the trials apply?

BACKGROUND: Asthma is a heterogeneous disease with a wide range of clinical phenotypes, not all of which may be encompassed in the subjects included in randomised controlled trials (RCTs). This makes it difficult for clinicians to know to what extent the evidence derived from RCTs applies to a given patient. AIM: To calculate the proportion of individuals with asthma who would have been eligible for the major asthma RCTs from the data of a random community survey of respiratory health. METHODS: A postal survey was sent to 3500 randomly selected individuals aged 25-75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function testing. Participants with current asthma were assessed against the eligibility criteria of the 17 major asthma RCTs cited in the Global Initiative for Asthma (GINA) guidelines. FINDINGS: A total of 749 participants completed the full survey, of whom 179 had current asthma. A median 4% of participants with current asthma (range 0-36%) met the eligibility criteria for the included RCTs. A median 6% (range 0-43%) of participants with current asthma on treatment met the eligibility criteria. INTERPRETATION: This study shows that the major asthma RCTs on which the GINA guidelines are based may have limited external validity as they have been performed on highly selected patient populations. Most of the participants with current asthma on treatment in the community would not have been eligible for these RCTs.

Adult↗

PubMed2006

Complete reference ranges for pulmonary function tests from a single New Zealand population.

AIM: Reference equations are prerequisites for interpretation of pulmonary function tests and are important in diagnosis, assessment, and management of a range of respiratory conditions. Such equations should be derived from populations who are closely ethnically and anthropomorphically matched to those in whom the equations will be used. This paper uses measurements from a single cohort of New Zealand adults to derive reference equations for all major pulmonary function tests. METHODS: Detailed pulmonary function test results including measurement of FEV6 and airway resistance were obtained from a cohort of 212 adult New Zealanders of European origin, who were never smokers with no respiratory disease or symptoms. Equations were developed by linear regression, including sex and other candidate variables based on prior univariate analysis. Comparisons between measured and predicted values using the reference equations of the European Respiratory Society (ERS) were made. RESULTS: Reference equations were produced with high values of explained variance (R2) for many commonly used clinical parameters. When compared with ERS equations, measured values for spirometry and most lung volumes were significantly higher than predicted (mean difference FEV1: male 0.48 L, female 0.36 L, mean difference TLC male 1.14 L, female 0.89 L, SVC male and female 0.66 L). CONCLUSIONS: This study provides a complete set of contemporary pulmonary function reference equations for a New Zealand population of European origin.

Adolescent↗

PubMed2006

Transcatheter aortic valve replacement in patients with critical aortic stenosis: rationale, device descriptions, early clinical experiences, and perspectives.

The development of lesser invasive transcatheter techniques for aortic valve replacement (AVR) to treat high surgical risk patients with severe aortic stenosis (AS) has engendered controversy among traditional cardiovascular therapists. Presently, there are two catheter-based treatment systems (the Cribier-Edwards Aortic Bioprosthesis and the CoreValve Revalving System) utilizing either a balloon-expandable or a self-expanding stent (or cage) platform which unfolds a pericardial tissue valve within the displaced diseased aortic valve. After ex vivo durability testing and animal studies, several clinical registries with these transcatheter AVR systems in almost 300 patients worldwide have demonstrated the following: (1) good acute hemodynamic performance with reduction in mean aortic valve gradients to <10 mm Hg; (2) frequent para-valvular regurgitation, which has improved with self-expanding devices and the use of larger (26 mm) valve sizes; (3) acceptable periprocedural (30-day) mortality (<10%) with the newest generation devices and improved operator techniques. Enlightened interdisciplinary treatment teams incorporating surgeons, interventionalists, and medical therapists as well as rigorously conducted randomized clinical trials will be required to determine if these innovative transcatheter AVR approaches will represent a viable therapy for high-risk patients with severe AS in the future.

Aortic Valve Insufficiency↗

PubMed2006

Evidence from Amazonian forests is consistent with isohydric control of leaf water potential.

Climate modelling studies predict that the rain forests of the Eastern Amazon basin are likely to experience reductions in rainfall of up to 50% over the next 50-100 years. Efforts to predict the effects of changing climate, especially drought stress, on forest gas exchange are currently limited by uncertainty about the mechanism that controls stomatal closure in response to low soil moisture. At a through-fall exclusion experiment in Eastern Amazonia where water was experimentally excluded from the soil, we tested the hypothesis that plants are isohydric, that is, when water is scarce, the stomata act to prevent leaf water potential from dropping below a critical threshold level. We made diurnal measurements of leaf water potential (psi 1), stomatal conductance (g(s)), sap flow and stem water potential (psi stem) in the wet and dry seasons. We compared the data with the predictions of the soil-plant-atmosphere (SPA) model, which embeds the isohydric hypothesis within its stomatal conductance algorithm. The model inputs for meteorology, leaf area index (LAI), soil water potential and soil-to-leaf hydraulic resistance (R) were altered between seasons in accordance with measured values. No optimization parameters were used to adjust the model. This 'mechanistic' model of stomatal function was able to explain the individual tree-level seasonal changes in water relations (r2 = 0.85, 0.90 and 0.58 for psi 1, sap flow and g(s), respectively). The model indicated that the measured increase in R was the dominant cause of restricted water use during the dry season, resulting in a modelled restriction of sap flow four times greater than that caused by reduced soil water potential. Higher resistance during the dry season resulted from an increase in below-ground resistance (including root and soil-to-root resistance) to water flow.

Brazil↗

PubMed2006

Duration of action of the salmeterol/fluticasone combination inhaler administered in the evening: a randomized controlled trial in childhood asthma.

OBJECTIVE AND BACKGROUND: To investigate the duration of bronchodilator action of a salmeterol/fluticasone combination (SFC) inhaler when administered in the evening to children with asthma. METHODOLOGY DESIGN: A double-blind, placebo-controlled, cross-over study. SETTING: Hospital inpatient. SUBJECTS: Fourteen children aged between 4 and 11 years with mild to moderate asthma (FEV(1) > 60% predicted) who exhibited a 15% increase in FEV(1) with bronchodilator. INTERVENTIONS: SUBJECTS inhaled, in random order, either SFC (100/50 microg) or placebo, via accuhaler, at 20.00 hours on two separate occasions with at least 3 days between study days. OUTCOME MEASURES: Lung function measurements including FEV(1), PEF, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity were measured at baseline, 2, 12, 16, 20 and 24 h. RESULTS: For all lung function parameters SFC resulted in significantly greater bronchodilation than placebo for at least 20 h after inhalation. At 24 h, the increase in FEV(1) and PEF compared with placebo was 0.08 L (95% confidence interval: -0.18 to 0.02, P = 0.16) and 27 L/min (95% confidence interval: -47 to -6, P = 0.004), respectively. CONCLUSIONS: The single administration of SFC via an accuhaler in the evening resulted in significant bronchodilation for at least 20 h in children with asthma.

Administration, Inhalation↗

PubMed2006

Mechanisms of atrial tachyarrhythmias following surgical atrial fibrillation ablation.

INTRODUCTION: Typical and atypical atrial flutters (AFLs) and atrial tachycardias (ATs) have been reported in patients with prior surgical atrial fibrillation ablation. The underlying mechanisms for this group of atrial tachyarrhythmias have not been well characterized and the efficacy of catheter ablation in their treatment is unknown. METHODS AND RESULTS: Twenty patients (6 females) with a surface ECG diagnosis of AFL or AT following surgical atrial fibrillation ablation underwent 26 electrophysiology studies. Patients manifesting sustained, organized, and beat-by-beat reproducible atrial electrical activity underwent complete right and left atrial catheter mapping and catheter ablation. One patient had no inducible tachyarrhythmia, while 5 patients had nonmappable arrhythmias. Nineteen of the 31 potentially mappable atrial tachyarrhythmias were completely characterized in 14 patients. The underlying mechanisms were macro-reentrant left AFL (n = 9), focal left AT (n = 3), typical right AFL (n = 6), and atypical right AFL (n = 1). Of the 19 completely characterized atrial arrhythmias, catheter ablation was performed for 18, and the procedure was successful for 13 of these. After a mean follow-up of 15 +/- 10 months, 15 of 20 patients (75%) were in sinus rhythm including 10 of 13 patients (77%) with AT/flutter ablation. Ten patients, including 6 following ablation, were maintaining sinus rhythm without antiarrhythmic medications. CONCLUSIONS: Patients with an ECG diagnosis of AFL or AT following surgical atrial fibrillation ablation may have multiple tachycardia mechanisms with the right or left atrium as the site of origin. Many of these rhythms may resolve with further maturation of surgical atrial fibrillation ablation (SAFA) lesions or be treatable with antiarrhythmic medication. However, persistent tachyarrhythmias can often be treated successfully with catheter mapping and ablation.

Atrial Fibrillation↗

PubMed2006

Off-pump epicardial atrial fibrillation surgery utilizing a novel bipolar radiofrequency system.

BACKGROUND: Over the past several years, pulmonary vein isolation for the treatment of atrial fibrillation has gained significant popularity. This study was undertaken to evaluate a novel radiofrequency (RF)-enabled clamp system designed to create transmural lesions epicardially on the beating heart using bipolar RF. METHODS: A set of differently shaped clamps modified to deliver bipolar RF energy were used to create a series of lesions in a beating heart canine model. The pulmonary veins and atrial appendages of 6 dogs were electrically isolated using bipolar RF energy. The right and left atrial appendages served as controls for the right and left pulmonary veins, respectively. Temperature-controlled RF energy was delivered to maintain a tissue temperature of 80 degrees C for 15 seconds. Electrical isolation was assessed acutely and after 4 weeks by a bipolar pacing protocol. RESULTS: A total of 24 circumferential lesions were created. By pacing analysis, 100% (24/24) of these lesions were electrically isolated acutely and 95% (19/20) were still isolated 4 weeks later. At 4 weeks, 92% (22/24) of lesions were transmural by histologic analysis, and 96% (23/24) demonstrated endocardial continuity. One animal experienced a fatal cardiac arrhythmia during initiation of the post-survival procedure, prior to electrophysiologic evaluation, accounting for the reduced number of potential electrically isolated lesions. CONCLUSION: Bipolar RF ablation utilizing a novel bipolar RF clamp device results in electrical isolation and histologic transmurality in an off-pump epicardial model.

Animals↗

PubMed2005

The 24 h duration of bronchodilator action of the budesonide/formoterol combination inhaler.

INTRODUCTION: The duration of bronchodilator action of the long-acting beta-agonist formoterol when administered in the evening has not been investigated. In this study we have investigated whether a single evening dose of formoterol, administered from the combination budesonide/formoterol (BUD/F) Turbuhaler significantly attenuates the circadian rhythm in airway tone over 24 h. METHODS: Twenty subjects with mild to moderate asthma (mean FEV1 84% predicted) participated in a double-blind, placebo-controlled, cross-over study. Subjects inhaled, in random order, placebo or BUD/F (2x100/6 microg) administered in the evening (2000 h) on two separate occasions. Lung function measurements including FEV1, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity (MEF(25-75%)) were assessed at baseline, at 1 h and subsequently every 4 h post-dose for 24 h. RESULTS: Compared with placebo, BUD/F significantly improved the three measures of airways function throughout the 24 h period, with a difference in FEV1 at 24 h of 0.20L (0.04-0.35L). BUD/F attenuated the biphasic pattern of the circadian rhythm in airway tone. CONCLUSION: The single evening administration of formoterol from the combination BUD/F inhaler resulted in a duration of bronchodilation of at least 24 h.

Administration, Inhalation↗

PubMed2004

Tight coupling between leaf area index and foliage N content in arctic plant communities.

The large spatial heterogeneity of arctic landscapes complicates efforts to quantify key processes of these ecosystems, for example productivity, at the landscape level. Robust relationships that help to simplify and explain observed patterns, are thus powerful tools for understanding and predicting vegetation distribution and dynamics. Here we present the same linear relationship between Leaf area index (LAI) and Total foliar nitrogen (TFN), the two factors determining the photosynthetic capacity of vegetation, across a wide range of tundra vegetation types in both northern Sweden and Alaska between leaf area indices of 0 and 1 m2 m(-2), which is essentially the entire range of leaf area index values for the Arctic as a whole. Surprisingly, this simple relationship arises as an emergent property at the plant community level, whereas at the species level a large variability in leaf traits exists. As the relationship between LAI and TFN exists among such varied ecosystems, the arctic environment must impose tight constraints on vegetation canopy development. This relationship simplifies the quantification of vegetation productivity of arctic vegetation types as the two most important drivers of productivity can be estimated reliably from remotely sensed NDVI images.

Alaska↗

PubMed2004

The 24 h duration of bronchodilator action of the salmeterol/fluticasone combination inhaler.

INTRODUCTION: The duration of bronchodilator action of the long-acting beta agonist salmeterol when administered in the evening has not been investigated. In this study we have investigated whether a single evening dose of salmeterol, administered from the combination salmeterol/fluticasone (SFC) Accuhaler significantly attenuates the circadian rhythm in airway tone over 24 h. METHODS: Eighteen subjects with mild to moderate asthma (mean FEV1 84% predicted) participated in a double-blind, double dummy, placebo controlled, cross-over study. Subjects inhaled, in random order, placebo, salbutamol (200 microg) or SFC (50/100 microg) administered in the evening (2000 h) on three separate occasions. Lung function measurements including FEV1, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity (MEF(25-75%)) were assessed at baseline, at 1 h and subsequently every 4 h post-dose for 24 h. RESULTS: Compared with placebo, SFC significantly improved the three measures of airways function throughout the 24 h period, with a difference in FEV1 at 24 h of 0.24 l (0.00-0.47 l). SFC abolished the biphasic pattern of the circadian rhythm in airway tone. In contrast, salbutamol had a significant bronchodilator action of 4-8 h, depending on the lung function parameter measured. CONCLUSION: The single evening administration of SFC via the Accuhaler resulted in a duration of bronchodilation of at least 24 h, with the abolition of the accentuated biphasic circadian variation in airway tone observed in asthma.

Administration, Inhalation↗

PubMed2003

Insertion of a left ventricular assist device in patients without thorough transplant evaluations: a worthwhile risk?

OBJECTIVES: Patients in acute cardiogenic shock may require placement of left ventricular assist devices before undergoing standard pretransplant evaluations. This practice raises ethical and logistic concerns and has led us to investigate the short- and long-term outcomes for this patient population. Methods and results We examined our adult bridge-to-transplant left ventricular assist device population over a 6-year period to characterize those patients with acute cardiogenic shock who received left ventricular assist devices on an emergency basis (ie, placement of a device within 24 hours of being listed for cardiac transplantation). Outcomes before and after transplant were compared with those of candidates with nonemergency evaluations by Kaplan-Meier survival curves and the Fisher exact test where appropriate. Of the 115 patients who required left ventricular assist device support, 73 (63%) patients required emergency placement; 70% of these patients survived to transplant compared with 83% of those with nonurgent device implantation (not statistically significant). Posttransplant survival curves were similar for patients with emergency device placement and those with nonurgent placement (not statistically significant). Twenty-two patients having emergency device placement did not undergo heart transplantation because of multisystem organ failure (14), device support withdrawal from irreversible neurologic injury (4), device or technical problems (2), and left ventricular assist device explant due to myocardial recovery (2). CONCLUSIONS: At our institution, the majority of left ventricular assist devices are placed on an emergency basis. Few of these patients require discontinuation of device support due to undetected conditions during abbreviated preoperative evaluation. Survival before and after transplant is comparable with those of patients who undergo nonurgent left ventricular assist device placement or medical therapy.

Adult↗

PubMed2002

Assessment of synchrony relationships between the native left ventricle and the HeartMate left ventricular assist device.

BACKGROUND: It has been suggested that the cardiac cycle becomes synchronized with the LVAD. Synchronization between the left ventricle and the LVAD may be important for ventricular unloading and coronary flow. In this study, we assessed the synchrony between the cardiac and LVAD cycles. METHODS: We studied 24 patients with HeartMate LVAD support. Native heart rate from an electrocardiogram and LVAD rate were measured at rest and peak exercise. Three patients underwent simultaneous invasive pressure measurement from the left ventricle and the aorta, and 3 patients underwent simultaneous recording of electrocardiogram and LVAD electrical signal. RESULTS: Resting heart rate was significantly higher than LVAD rate (96 +/- 17 vs 66 +/- 15 beats [b]/min, p < 0.0001), with no correlation between the 2 (r = 0.25). Peak heart rate was significantly higher than LVAD rate (142 +/- 16 vs 102 +/- 14 b/min, p < 0.0001), with no correlation observed (r = 0.31). Electrical signal recording confirmed the absence of cardiac-LVAD synchrony. Pressure measurements revealed a cyclical intraventricular pressure variation, determined by the relationship between the cardiac and LVAD cycles. Intraventricular pressure was lowest when left ventricular systole occurred during pump filling and highest when left ventricular systole occurred during pump ejection. CONCLUSIONS: The cardiac and LVAD cycles are not in synchrony at rest or at peak exercise. However, a cyclical variation in left ventricular pressure exists, dependent upon the phasic relationship of the cardiac-LVAD cycles, which significantly effects ventricular loading. Better understanding of this relationship may be important in developing assist devices for optimal left ventricular unloading and improvement of myocardial recovery.

Adult↗

PubMed2002

Thyroidectomy using local anesthesia in critically ill patients with amiodarone-induced thyrotoxicosis: a review and description of the technique.

Hyperthyroidism caused by amiodarone is a well-known and accepted side effect of therapy. This problem can frequently be treated by medical means if patients are stable. In some patients, particularly those who are critically ill with cardiac disease the addition of hyperthyroidism can be particularly detrimental. These patients present with an interesting paradox because they are frequently on amiodarone because of life-threatening arrhythmias not responsive to other regimens, yet the amiodarone can precipitate hyperthyroidism that can acutely worsen the progression of their disease and prevalence of arrhythmias. In these patients, prompt treatment of their hyperthyroidism by total thyroidectomy may be the best option. Unfortunately, this also raises another treatment paradox in that these patients are at particularly high risk for complications from general anesthesia. In this subset of patients, total thyroidectomy under local anesthesia may be the best treatment option. Herein, we present a review of amiodarone-induced hyperthyroidism and our technique and review of our experience in its management with total thyroidectomy performed under local anesthesia.

Adult↗

PubMedDate not supplied

Minimally invasive surgery for atrial fibrillation: toward a totally endoscopic, beating heart approach.

In the last several years, a number of procedures have been conceived that have attempted to treat atrial fibrillation (AF) by creating a limited set of lesions modeled after those of the Maze operation. These lesions have been created by a variety of means, including the traditional cut-and-sew method, but also by nonincisional techniques. These have included cryoablation as well as several thermal techniques, using radiofrequency, microwave, laser, and focused ultrasound energy. One reason for the development of these nonincisional techniques has been the desire to develop less invasive operations for the treatment of AF. The specific goal of our center has been to utilize these energy sources as well as other minimally invasive tools, such as surgical robots, to develop a closed chest, off-pump procedure for AF. The development of such a procedure is outlined in this article.

Atrial Appendage↗