Bronchial thermoplasty increases airway volume measured by functional respiratory imaging.

BACKGROUND: The purpose of this study was to use CT scanning with computational fluid dynamics to evaluate the mechanisms by which Bronchial Thermoplasty (BT) improves asthmatic symptoms. METHODS: The study was conducted in a university teaching hospital, experienced in performing BT. Imaging studies were performed before, and after, BT of the left lung, and prior to treatment of the right lung, which therefore acted as a control. On each occasion, two high-resolution CT scans were performed, one at full inspiration (TLC) and the other at Functional Residual Capacity (FRC). The study protocol was offered to 10 patients, all of whom met the definition of severe asthma, despite high dose inhaled corticosteroids and dual long acting bronchodilators. RESULTS: Significant increases in airway luminal volume were observed on the treated side, compared with control, at both full inspiration (by 27%) and at FRC (by 17%). The ratio of distal airway volume to lung volume significantly increased on the treated side. The change in airway volume with inspiration from FRC increased by 48% on the treated side compared to 5% in the control lung, suggesting treatment increased airway distensibility. No effect was observed on airway wall thickness, nor air trapping. There was a trend towards correlation between the improvement in airway volume at TLC and improvement in symptoms. CONCLUSION: This study demonstrates that BT increases the luminal airway volume on the treated side compared to the control lung. We suggest that this is an important link between the airway smooth muscle atrophy demonstrated pathologically, and the improvement in symptoms observed clinically.

Working while unwell: Workplace impairment in people with severe asthma.

BACKGROUND: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. OBJECTIVE: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. METHODS: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. RESULTS: At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). CONCLUSION AND CLINICAL RELEVANCE: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.

Real-life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria.

BACKGROUND: Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30-1500 IU/mL) and bodyweight (30-150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR). OBJECTIVES: To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. METHODS: Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). RESULTS: Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria; other characteristics were similar to within-range participants. Above-range participants had higher baseline IgE [812 (IQR 632, 1747) IU/mL vs. 209 (IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 (IQR 650, 750) mg] compared to within-range participants [450 (IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire (ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P < 0.0001 for both) and Asthma Quality of Life Questionnaire (AQLQ mean score (3.22 up to 4.41 for above-range, 3.71 up to 4.88 for within-range, P < 0.0001) were observed in both groups. Forced expiratory volume in one second (FEV1 ) improved among above-range participants. There was no difference in response between above-range and within-range participants. Above-range participants due to either IgE alone or IgE and weight had similar improvements in ACQ-5, AQLQ and FEV1 . CONCLUSIONS AND CLINICAL RELEVANCE: Patients with severe allergic asthma above recommended dosing criteria for omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range participants, achieved without dose escalation above 750 mg.

Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry.

BACKGROUND: Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway; however, effectiveness data in a population with significant comorbidities are limited. AIMS: To describe severe allergic asthma, omalizumab treatment outcomes and predictors of response among the Australian Xolair Registry participants. METHODS: A web-based post-marketing surveillance registry was established to characterise the use, effectiveness and adverse effects of omalizumab (Xolair) for severe allergic asthma. RESULTS: Participants (n = 192) (mean age 51 years, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed, and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56) and significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57), and 52% were using daily oral corticosteroid (OCS). Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. OCS use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 ≥ 2.0 (P = 0.002) and older age (P = 0.05) predicted the magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2) and chest pains (n = 1). CONCLUSION: Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting.

Therapeutic response to bronchial thermoplasty: toward feasibility of patient selection based on modeling predictions.

Bronchial thermoplasty (BT) is a treatment for moderate-to-severe asthma in which the airway smooth muscle layer is targeted directly using thermal ablation. Although it has been shown to be safe and effective in long-term follow-up, questions remain about its mechanism of action, patient selection, and optimization of protocol based on structural phenotype. Using a cohort of 20 subjects who underwent thermoplasty and assessment by computed tomography (CT), we demonstrate that response to BT can be feasibly predicted based on pretreatment airway dimensions that inform a subject-specific computational model. Analysis revealed the need for CT assessment at total lung capacity, rather than functional residual capacity, which was less sensitive to the effects of BT. Final model predictions compared favorably with observed outcomes in terms of airway caliber and asthma control, suggesting that this approach could form the basis of improved clinical practice.NEW & NOTEWORTHY Bronchial thermoplasty is a treatment for asthma that targets the airway smooth muscle directly. We demonstrate the feasibility and constraints of predicting patient-specific response to thermoplasty using a computational model informed by pretreatment CT scans at different lung volumes. Predictions are compared with functional outcomes and posttreatment CT scans. This has the potential to form the basis for improved clinical practice.

Cemented Exeter total hip arthroplasty with a 32 mm head on highly crosslinked polyethylene: Does age influence functional outcome, satisfaction, activity, stem migration, and periprosthetic bone mineral density?

OBJECTIVES: Our primary aim was to describe migration of the Exeter stem with a 32 mm head on highly crosslinked polyethylene and whether this is influenced by age. Our secondary aims were to assess functional outcome, satisfaction, activity, and bone mineral density (BMD) according to age. PATIENTS AND METHODS: A prospective cohort study was conducted. Patients were recruited into three age groups: less than 65 years (n = 65), 65 to 74 years (n = 68), and 75 years and older (n = 67). There were 200 patients enrolled in the study, of whom 115 were female and 85 were male, with a mean age of 69.9 years (sd 9.5, 42 to 92). They were assessed preoperatively, and at three, 12 and, 24 months postoperatively. Stem migration was assessed using Einzel-Bild-Röntgen-Analyse (EBRA). Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), EuroQol-5 domains questionnaire (EQ-5D), short form-36 questionnaire (SF-36,) and patient satisfaction were used to assess outcome. The Lower Extremity Activity Scale (LEAS), Timed Up and Go (TUG) test, and activPAL monitor (energy expelled, time lying/standing/walking and step count) were used to assess activity. The BMD was assessed in Gruen and Charnley zones. RESULTS: Mean varus/valgus tilt was -0.77° and axial subsidence was -1.20 mm. No significant difference was observed between age groups (p ⩾ 0.07). There was no difference according to age group for postoperative WOMAC (p ⩾ 0.11), HHS (p ⩾ 0.06), HOOS (p ⩾ 0.46), EQ-5D (p ⩾ 0.38), patient satisfaction (p ⩾ 0.05), or activPAL (p ⩾ 0.06). Patients 75 years and older had a worse SF-36 physical function (p = 0.01) and physical role (p = 0.03), LEAS score (p < 0.001), a shorter TUG (p = 0.01), and a lower BMD in Charnley zone 1 (p = 0.02). CONCLUSION: Exeter stem migration is within normal limits and is not influenced by age group. Functional outcome, patient satisfaction, activity level, and periprosthetic BMD are similar across all age groups.Cite this article: N. D. Clement, M. Bardgett, K. Merrie, S. Furtado, R. Bowman, D. J. Langton, D. J. Deehan, J. Holland. Cemented Exeter total hip arthroplasty with a 32 mm head on highly crosslinked polyethylene: Does age influence functional outcome, satisfaction, activity, stem migration, and periprosthetic bone mineral density? Bone Joint Res 2019;8:275-287. DOI: 10.1302/2046-3758.86.BJR-2018-0300.R1.

Is the synovial fluid cobalt-to-chromium ratio related to the serum partitioning of metal debris following metal-on-metal hip arthroplasty?

OBJECTIVES: We investigated the reliability of the cobalt-chromium (CoCr) synovial joint fluid ratio (JFR) in identifying the presence of a severe aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response and/or suboptimal taper performance (SOTP) following metal-on-metal (MoM) hip arthroplasty. We then examined the possibility that the CoCr JFR may influence the serum partitioning of Co and Cr. METHODS: For part A, we included all revision surgeries carried out at our unit with the relevant data, including volumetric wear analysis, joint fluid (JF) Co and Cr concentrations, and ALVAL grade (n = 315). Receiver operating characteristic curves were constructed to assess the reliability of the CoCr JFR in identifying severe ALVAL and/or SOTP. For part B, we included only patients with unilateral prostheses who had given matched serum and whole blood samples for Co and Cr analysis (n = 155). Multiple regression was used to examine the influence of JF concentrations on the serum partitioning of Co and Cr in the blood. RESULTS: A CoCr JFR > 1 showed a specificity of 83% (77% to 88%) and sensitivity of 63% (55% to 70%) for the detection of severe ALVAL and/or SOTP. In patients with CoCr JFRs > 1, the median blood Cr to serum Cr ratio was 0.99, compared with 0.71 in patients with CoCr JFRs < 1 (p < 0.001). Regression analysis demonstrated that the blood Cr to serum Cr value was positively associated with the JF Co concentration (p = 0.011) and inversely related to the JF Cr concentration (p < 0.001). CONCLUSION: Elevations in CoCr JFRs are associated with adverse biological (severe ALVAL) or tribocorrosive processes (SOTP). Comparison of serum Cr with blood Cr concentrations may be a useful additional clinical tool to help to identify these conditions.Cite this article: D. J. Langton, S. Natu, C. F. Harrington, J. G. Bowsher, A. V. F. Nargol. Is the synovial fluid cobalt-to-chromium ratio related to the serum partitioning of metal debris following metal-on-metal hip arthroplasty? Bone Joint Res 2019;8:146-155. DOI: 10.1302/2046-3758.83.BJR-2018-0049.R1.

Aseptic lymphocyte-dominated vasculitis-associated lesions are related to changes in metal ion handling in the joint capsules of metal-on-metal hip arthroplasties.

OBJECTIVES: We have encountered patients who developed large joint fluid collections with massive elevations in chromium (Cr) and cobalt (Co) concentrations following metal-on-metal (MoM) hip arthroplasties. In some cases, retrieval analysis determined that these ion concentrations could not be explained simply by the wear rates of the components. We hypothesized that these effects may be associated with aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL). PATIENTS AND METHODS: We examined the influence of the ALVAL grade on synovial fluid Co and Cr concentrations following adjustment for patient and device variables, including volumetric wear rates. Initially restricting the analysis to include only patients with one MoM hip resurfacing device, we performed multiple regression analyses of prospectively collected data. We then repeated the same statistical approach using results from a larger cohort with different MoM designs, including total hip arthroplasties. RESULTS: In the resurfacing cohort (n = 76), the statistical modelling indicated that the presence of severe ALVAL and a large fluid collection were associated with greater joint fluid Co concentrations after adjustment for volumetric wear rates (p = 0.005). These findings were replicated in the mixed implant group (n = 178), where the presence of severe ALVAL and a large fluid collection were significantly associated with greater fluid Co concentrations (p < 0.001). CONCLUSION: The development of severe ALVAL is associated with elevations in metal ion concentrations far beyond those expected from the volumetric loss from the prosthetic surfaces. This finding may aid the understanding of the sequence of events leading to soft-tissue reactions following MoM hip arthroplasties.Cite this article: D. J. Langton, R. P. Sidaginamale, T. J. Joyce, J. G. Bowsher, J. P. Holland, D. Deehan, A. V. F. Nargol, S. Natu. Aseptic lymphocyte-dominated vasculitis-associated lesions are related to changes in metal ion handling in the joint capsules of metal-on-metal hip arthroplasties. Bone Joint Res 2018;7:388-396. DOI: 10.1302/2046-3758.76.BJR-2018-0037.

Material loss at the femoral head taper: a comparison study of the Exeter metal-on-polyethylene and contemporary metal-on-metal total hip arthroplasty.

AIMS: There are limited published data detailing the volumetric material loss from tapers of conventional metal-on-polyethylene (MoP) total hip arthroplasties (THAs). Our aim was to address this by comparing the taper wear rates measured in an explanted cohort of the widely used Exeter THA with those measured in a group of metal-on-metal (MoM) THAs. PATIENTS AND METHODS: We examined an existing retrieval database to identify all Exeter V40 and Universal MoP THAs. Volumetric wear analysis of the taper surfaces was conducted using previously validated methodology. These values were compared with those obtained from a series of MoM THAs using non-parametric statistical methodology. A number of patient and device variables were accounted for using multiple regression modelling. RESULTS: A total of 95 Exeter MoP and 249 MoM THAs were examined. The median volumetric loss from the MoM cohort was over four times larger than that from the MoP cohort (1.01 mm3 vs 0.23 mm3, p < 0.001), despite a significantly shorter median period in vivo for the MoM group (48 months vs 90 months, p < 0.001). Multiple regression modelling indicated that the dominant variables leading to greater female taper material loss were bearing diameter (p < 0.001), larger female taper angles (p < 0.001), and male titanium stem tapers (p < 0.001). CONCLUSION: Consistent with the long-term clinical success of the device, the volumetric material loss from Exeter femoral head tapers was, in general, small compared with that from larger-diameter MoM head tapers. Cite this article: Bone Joint J 2018;100-B:1310-9.

Explant analysis of the Biomet Magnum/ReCap metal-on-metal hip joint.

OBJECTIVES: The high revision rates of the DePuy Articular Surface Replacement (ASR) and the DePuy ASR XL (the total hip arthroplasty (THA) version) have led to questions over the viability of metal-on-metal (MoM) hip joints. Some designs of MoM hip joint do, however, have reasonable mid-term performance when implanted in appropriate patients. Investigations into the reasons for implant failure are important to offer help with the choice of implants and direction for future implant designs. One way to assess the performance of explanted hip prostheses is to measure the wear (in terms of material loss) on the joint surfaces. METHODS: In this study, a coordinate measuring machine (CMM) was used to measure the wear on five failed cementless Biomet Magnum/ReCap/ Taperloc large head MoM THAs, along with one Biomet ReCap resurfacing joint. Surface roughness measurements were also taken. The reason for revision of these implants was pain and/or adverse reaction to metal debris (ARMD) and/or elevated blood metal ion levels. RESULTS: The mean wear rate of the articulating surfaces of the heads and acetabular components of all six joints tested was found to be 6.1 mm3/year (4.1 to 7.6). The mean wear rate of the femoral head tapers of the five THAs was 0.054 mm3/year (0.021 to 0.128) with a mean maximum wear depth of 5.7 µm (4.3 to 8.5). CONCLUSION: Although the taper wear was relatively low, the wear from the articulating surfaces was sufficient to provide concern and was potentially large enough to have been the cause of failure of these joints. The authors believe that patients implanted with the ReCap system, whether the resurfacing prosthesis or the THA, should be closely monitored.Cite this article: S. C. Scholes, B. J. Hunt, V. M. Richardson, D. J. Langton, E. Smith, T. J. Joyce. Explant analysis of the Biomet Magnum/ReCap metal-on-metal hip joint. Bone Joint Res 2017;6:113-122. DOI: 10.1302/2046-3758.62.BJR-2016-0130.R2.

A comparison study of stem taper material loss at similar and mixed metal head-neck taper junctions.

AIMS: We sought to determine whether cobalt-chromium alloy (CoCr) femoral stem tapers (trunnions) wear more than titanium (Ti) alloy stem tapers (trunnions) when used in a large diameter (LD) metal-on-metal (MoM) hip arthroplasty system. PATIENTS AND METHODS: We performed explant analysis using validated methodology to determine the volumetric material loss at the taper surfaces of explanted LD CoCr MoM hip arthroplasties used with either a Ti alloy (n = 28) or CoCr femoral stem (n = 21). Only 12/14 taper constructs with a rough male taper surface and a nominal included angle close to 5.666° were included. Multiple regression modelling was undertaken using taper angle, taper roughness, bearing diameter (horizontal lever arm) as independent variables. Material loss was mapped using a coordinate measuring machine, profilometry and scanning electron microscopy. RESULTS: After adjustment for other factors, CoCr stem tapers were found to have significantly greater volumetric material loss than the equivalent Ti stem tapers. CONCLUSION: When taper junction damage is identified during revision of a LD MoM hip, it should be suspected that a male taper composed of a standard CoCr alloy has sustained significant changes to the taper cone geometry which are likely to be more extensive than those affecting a Ti alloy stem. Cite this article: Bone Joint J 2017;99-B:1304-12.

The clinical implications of metal debris release from the taper junctions and bearing surfaces of metal-on-metal hip arthroplasty: joint fluid and blood metal ion concentrations.

AIMS: We wished to investigate the influence of metal debris exposure on the subsequent immune response and resulting soft-tissue injury following metal-on-metal (MoM) hip arthroplasty. Some reports have suggested that debris generated from the head-neck taper junction is more destructive than equivalent doses from metal bearing surfaces. PATIENTS AND METHODS: We investigated the influence of the source and volume of metal debris on chromium (Cr) and cobalt (Co) concentrations in corresponding blood and hip synovial fluid samples and the observed agglomerated particle sizes in excised tissues using multiple regression analysis of prospectively collected data. A total of 199 explanted MoM hips (177 patients; 132 hips female) were analysed to determine rates of volumetric wear at the bearing surfaces and taper junctions. RESULTS: The statistical modelling suggested that a greater source contribution of metal debris from the taper junction was associated with smaller aggregated particle sizes in the local tissues and a relative reduction of Cr ion concentrations in the corresponding synovial fluid and blood samples. Metal debris generated from taper junctions appears to be of a different morphology, composition and therefore, potentially, immunogenicity to that generated from bearing surfaces. CONCLUSION: The differences in debris arising from the taper and the articulating surfaces may provide some understanding of the increased incidence of soft-tissue reactions reported in patients implanted with MoM total hip arthroplasties compared with patients with hip resurfacings. Cite this article: Bone Joint J 2016;98-B:925-33.

Guidelines for the management of hepatitis C in general practice: a semi-qualitative interview survey of GPs' views regarding content and implementation.

BACKGROUND: Hepatitis C is a common infection among people who attend GPs for methadone maintenance treatment. AIM: To determine the views of GPs towards clinical guidelines for the management of hepatitis C among current or former injecting drug users in advance of their implementation. METHODS: A purposive sample of 14 GPs (10% of the total prescribing methadone at the time the guidelines were developed) was invited to review a pre-publication draft of the guidelines and interviewed regarding content, presentation, perceived barriers to implementation and suggested interventions to facilitate effective implementation of the guidelines. RESULTS: GPs indicated the guidelines were useful but suggested aspects of presentation should be clarified. Organisational issues were identified as the principal barriers to effective implementation, with the provision of additional nursing support the principal intervention suggested to facilitate implementation. CONCLUSIONS: Interviewing intended recipients may be an important step in ensuring clinical practice guidelines are effectively implemented.

Experience of hepatitis C among current or former heroin users attending general practice.

The majority of injecting drug users in Ireland are infected with hepatitis C (HCV) and many attend general practice for methadone maintenance treatment. To describe awareness and experience of HCV infection, related investigations and treatment, a semi-qualitative interview study of current or former heroin users attending a general practice was carried out. Twenty-five patients (69% of total) were interviewed, of whom 23 were on methadone maintenance therapy at the time of the interview and 22 were HCV positive. While awareness of harm reduction measures and health implications of the infection was good, continued high-risk activity was common. Negative experiences at diagnosis, of subsequent investigations and treatments received were common. Only one person had been treated for HCV. We conclude there are a number of barriers to effective HCV management among heroin users and further research is needed to improve our understanding of this issue.

Cardiovascular responses to graded treadmill exercise during the development of doxorubicin induced heart failure in rabbits.

STUDY OBJECTIVE: The aim was to examine the haemodynamic and humoral responses to graded treadmill exercise, serially during the development of congestive heart failure. DESIGN: Doxorubicin (1 mg.kg-1) was given to rabbits twice weekly intravenously over 8 weeks to induce a low output congestive cardiomyopathy. Treadmill exercise at 8 and 16 m.min-1 was performed at weeks 0, 2, 4, 6, 7, and 8. During each exercise study, continuous recordings were made of cardiac output, mean arterial pressure, and heart rate, and central venous blood was sampled at rest and during the last 10 s of exercise for plasma noradrenaline and plasma renin activity. EXPERIMENTAL MATERIAL: Six cross-bred English rabbits, mean weight 2.6 kg, received doxorubicin treatment; three control rabbits received vehicle injection. MEASUREMENTS AND MAIN RESULTS: Over the first 2 weeks, resting haemodynamic variables and responses to exercise were normal in all rabbits. Thereafter, doxorubicin treated rabbits had progressive falls in resting cardiac index and mean arterial pressure, and rises in resting heart rate and systemic vascular resistance. The normal increases in cardiac index and mean arterial pressure with exercise were progressively attenuated, despite an increase in resting and exercising heart rate. The resting levels of plasma noradrenaline and plasma renin rose after the fourth week of doxorubicin treatment. Throughout the experiment, exercise consistently raised plasma noradrenaline and renin, but the exercising levels of both hormones increased as heart failure progressed. Four of the six doxorubicin treated rabbits became exhausted in the final run and there was an intense rise in systemic vascular resistance. CONCLUSIONS: In this rabbit model of chronic heart failure, sympathetic vasoconstrictor drive is greater than normal at rest, and is greatly exaggerated during exercise. It is suggested that this abnormal response to exercise results from a combination of failure of arterial pressure to reach the elevated set point of the arterial baroreflex, increased afferent input from exercising muscles due to their underperfusion, and increase in central command due to muscle fatigue.

Association of treponeme species with atypical foot lesions in goats.

Five UK goat farms with high levels of lameness (prevalence 14-67 per cent) were investigated. On two farms (farms 1 and 2), the animals presented with typical footrot lesions. The remaining three farms (farms 3, 4 and 5) presented with infected lesions on the foot that did not resemble footrot. These lesions were observed to start from the white line or sole but the interdigital space was rarely affected. Swabs were processed by PCR to assess the presence of Dichelobacter nodosus and three specific treponeme groups (group 1: Treponema medium/Treponema vincentii-like, group 2: Treponema phagedenis-like and group 3: Treponema denticola/Treponema putidum-like) that are reported to be associated with bovine digital dermatitis and contagious ovine digital dermatitis. On farms 1 and 2, 85.7 per cent of samples were found to be positive for D nodosus while only 9.5 per cent were positive for treponeme groups 1, 2 and 3. In contrast, 5.3 per cent of samples from farms 3, 4 and 5 were positive for D nodosus, while 34.2, 68.4 and 36.8 per cent of samples from these farms tested positive for treponeme groups 1, 2 and 3, respectively. T medium/T vincentii-like, T phagedenis-like and T denticola/T putidum-like treponemes were detected on foot lesions of lame goats suggesting that they have a role in the aetiology of this lameness, which has not previously been described in dairy goats.

Comparison of felodipine extended release and conventional tablets in essential hypertension using ambulatory blood pressure monitoring.

Two formulations of felodipine, conventional and extended release (ER) tablets, were compared in a double-blind, crossover study of patients whose blood pressure was not being controlled using metoprolol 100 mg once daily. Nineteen patients with a supine diastolic blood pressure greater than or equal to 95 mmHg after 4 weeks of taking metoprolol and placebo were randomly assigned to felodipine conventional (5 mg twice a day) or ER (10 mg once daily) for 4 weeks. A 2-week washout period was then followed by 4 weeks of treatment with the alternative formulation. Metoprolol once daily was taken concomitantly throughout the study. Clinic blood pressure was measured at 0 h (i.e. 12 h after the last dose of conventional, and 24 h after the last ER felodipine dose), and then 2 and 5 h after the following dose had been taken. Ambulatory blood pressure and the heart rate were monitored over 24 h using an Accutracker (Suntech Medical Instruments, Raleigh, North Carolina, USA). During the final treatment, both felodipine formulations caused similar substantial falls in supine blood pressure compared with pressures prior to randomized treatment. The falls in clinic blood pressures (systolic/diastolic) were similar with the conventional and ER formulations at all time points, i.e. 0 h (21/13; 19/11 mmHg), 2 h (39/18; 36/18 mmHg) and 5 h (30/12; 35/11 mmHg) after the morning dose was taken. Both formulations also produced similar falls in blood pressures over 24 h and during the daytime (21/12; 20/12 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Experience of heroin overdose among drug users attending general practice.

BACKGROUND: Heroin overdose is responsible for significant mortality. It has not previously been highlighted as an important prevention or care issue for general practitioners (GPs) involved in the management of drug misuse. AIMS: To examine the prevalence and experience of heroin overdose in a population of drug users attending a general practice. METHOD: A questionnaire-based interview of drug users attending a general practice in Dublin, Ireland. RESULTS: Twenty-four (73% of estimated total) drug users were interviewed. Although 17 (71%) were on recognised methadone treatment programmes, 10 (42%) were still injecting heroin. A total of 23 (96%) had witnessed an overdose, with 10 (42%) having been victims of overdose themselves. Twenty-two (92%) knew a victim of fatal overdose, with four (17%) having been present at a fatal overdose. The interviews revealed high levels of activity associated with overdose and poor use of preventive measures. CONCLUSION: The issue of prevention and management of overdose should become a priority for GPs caring for opiate-dependent patients.

Comparison of bone mineral density and quantitative ultrasound of the calcaneus: site-matched correlation and discrimination of axial BMD status.

The performance of quantitative ultrasound (QUS) and dual energy X-ray absorptiometry (DXA) bone densitometry of the calcaneus have been compared, both in terms of site-matched correlation and their discriminatory ability to identify osteoporotic and osteoporotic or osteopenic subjects. 91 female subjects (aged 56.9 +/- 9.6 years, 31-84 years) who were routinely referred for axial BMD assessment of the lumbar spine and femoral neck by DXA (Lunar DPX-L), consented to have additional measurements of QUS (McCue CubaClinical Mk II) and DXA (Lunar PIXI) of their left calcaneus. The site-matched correlation between calcaneal BMD with QUS parameters were: (a) broadband ultrasound attenuation (BUA) alone, adj-R2 = 62.7%, p < 0.0001; (b) velocity (VOS) alone, adj-R2 = 48.4%, p < 0.0001; and (c) BUA and VOS combined, adj-R2 = 65.2%, p < 0.0001. The site-matched correlations are towards the higher end of data reported by other researchers, indicative of the exacting measurement protocol implemented here. 30 subjects were categorized as normal, 38 being osteopenic and 23 being osteoporotic. Optimum accuracies and odds ratios were obtained using logistic regression. The differences in accuracy between calcaneal BMD and calcaneal QUS parameters were statistically insignificant, with zero included within the confidence intervals, for the identification of both (a) osteoporotic and (b) osteoporotic or osteopenic subjects. The odds ratios for the discrimination of subject status achieved with calcaneal BMD were higher, although statistically insignificant, than achieved with the QUS parameters. Receiver operator characteristic (ROC) analysis for the identification of subjects into the categories (a) and (b) above was performed. Areas under the ROC curve (AUC) (95% confidence intervals) for the logit of the probability that a subject would be osteoporotic were: 0.814 (0.700, 0.928) for calcaneal BMD; 0.791 (0.673, 0.909) for BUA; 0.717 (0.588, 0.846) for VOS; and 0.793 (0.675, 0.911) for BUA and VOS combined. For the identification of osteoporotic or osteopenic subjects, the ROC areas were: 0.851 (0.774, 0.928) for calcaneal BMD; 0.773 (0.678, 0.868) for BUA; 0.783 (0.690, 0.877) for VOS; and 0.778 (0.685, 0.871) for BUA and VOS combined. Again, calcaneal BMD provided a higher, yet statistically insignificant, AUC than any QUS parameter. In conclusion, for the identification of subjects defined by World Health Organization criteria for axial BMD, the performance of BMD and QUS calcaneal parameters were statistically comparable. The choice of peripheral bone densitometry modality should therefore be made upon factors external to their discriminatory performance.

Male and female normative data for ultrasound measurement of the calcaneus within the UK adult population.

The establishment of accurate normative data for specific populations is required before ultrasound bone densitometry may be considered for routine clinical application. A single general practice was utilized, representing both rural and urban populations, to recruit 169 male and 210 female subjects in the age range 20-80 years. Measurements of broadband ultrasound attenuation (BUA) and velocity (VOS) of the left calcaneus were undertaken using the McCue CUBAClinical II system. Two descriptive statistical models were used, mean and 95th percentile, and regression analysis. The female data for both BUA and VOS illustrated peak values in the 30-39 years age group, falling steadily thereafter. For male BUA and VOS data there was less evidence of an age related dependence. Upon analysis of previous normative studies and current data it is evident that there is considerable variability. In addition to different commercial systems being utilized, there is a lack of consistency in study design and method of subject recruitment. The need for accurate calibration and cross-calibration methods for commercial ultrasound bone densitometers is therefore of paramount importance to enable clinical interpretation of ultrasound measurements to be performed.