antigen measurements, thus increasing costs substantially. It may be that this cost would be just... more antigen measurements, thus increasing costs substantially. It may be that this cost would be justifiable if the result was a reinvigoration of flagging sexual appetites, physical strength and general wellbeing of an ageing male population, as they face more years in the workforce before retirement. For now the case is far from proven. Adopting a single cutoff for reporting serum testosterone in males, irrespective of age, may contribute substantially to the widespread use of an expensive treatment with unproven safety and efficacy. We believe that biochemistry departments should report age-related reference intervals for total and (calculated) free testosterone, thus enabling identification of individuals with significant testosterone deficiency who are likely to benefit from replacement therapy.
The term 'big data' is used to refer both to data-sets and to how the data are analysed and used.... more The term 'big data' is used to refer both to data-sets and to how the data are analysed and used. The data may be heterogeneous and complex and may change or accumulate rapidly. A given data-set may combine many different databases, so connecting them together can present a big challenge.
Background: We aimed to investigate in patients with type 2 diabetes whether aortic stiffness is:... more Background: We aimed to investigate in patients with type 2 diabetes whether aortic stiffness is: (i) associated with glycaemic control, (ii) associated with adverse outcomes and (iii) can be reversed on treatment with RAAS inhibition. Methods: Patients with type 2 diabetes (N = 94) and low vascular risk underwent assessment of cardiovascular risk and CMR assessment of ascending aortic distensibility (AAD), descending aortic distensibility (DAD) and aortic pulse wave velocity (PWV). Of these patients a subgroup with recent onset microalbuminuria (N = 25) were treated with renin-angiotensin-aldosterone system (RAAS) inhibition and imaging repeated after 1 year. All 94 patients were followed up for 2.4 years for major adverse cardiovascular disease (CVD) events including myocardial infarction detected on late gadolinium enhancement CMR. Results: Ascending aortic distensibility, DAD and PWV all had a significant association with age and 24 h systolic blood pressure but only AAD had a significant association with glycaemic control, measured as HbA1c (Beta − 0.016, P = 0.04). The association between HbA1c and AAD persisted even after correction for age and hypertension. CVD events occurred in 19/94 patients. AAD, but not DAD or PWV, was associated with CVD events (hazard ratio 0.49, 95% confidence interval 0.25-0.95, P = 0.01). On treatment with RAAS inhibition, AAD, but not DAD or PWV, showed significant improvement from 1.51 ± 1.15 to 1.97 ± 1.07 10 −3 mmHg −1 , P = 0.007. Conclusions: Ascending aortic distensibility measured by CMR is independently associated with poor glycaemic control and adverse cardiovascular events. Furthermore it may be reversible on treatment with RAAS inhibition. AAD is a promising marker of cardiovascular risk in asymptomatic patients with type 2 diabetes and has potential use as a surrogate cardiovascular endpoint in studies of novel hypoglycaemic agents.
Immunoassay methods for prolactin detect macroprolactin (i.e. high molecular mass complexes of pr... more Immunoassay methods for prolactin detect macroprolactin (i.e. high molecular mass complexes of prolactin) to various degrees. Therefore it is generally assumed that the widely differing results by methods that measure both moieties to a differing extent are due to the presence of macroprolactin. We present a case which challenges such an assumption and suggest that precipitation by polyethylene glycol is the most reliable screen for identifying macroprolactin (and/or interfering antibodies if present).
The reference intervals (RIs) given in laboratory reports have an important role in aiding clinic... more The reference intervals (RIs) given in laboratory reports have an important role in aiding clinicians in interpreting test results in reference to values of healthy populations. In this report, we present a proposed protocol and standard operating procedures (SOPs) for common use in conducting multicenter RI studies on a national or international scale. The protocols and consensus on their contents were refined through discussions in recent C-RIDL meetings. The protocol describes in detail (1) the scheme and organization of the study, (2) the target population, inclusion/ exclusion criteria, ethnicity, and sample size, (3) health status questionnaire, (4) target analytes, (5) blood collection, (6) sample processing and storage, (7) assays, (8) cross-check testing, (9) ethics, (10) data analyses, and (11) reporting of results. In addition, the protocol proposes the common measurement of a panel of sera when no standard materials exist for harmonization of test results. It also describes the requirements of the central laboratory, including the method of cross-check testing between the central laboratory of each country and local laboratories. This protocol and the SOPs remain largely exploratory and may require a reevaluation from the practical point of view after their implementation in the ongoing worldwide study. The paper is mainly intended to be a basis for discussion in the scientific community.
European Heart Journal - Quality of Care and Clinical Outcomes, Nov 19, 2018
The UK National Institute for Health and Care Excellence (UK-NICE) and European Society of Cardio... more The UK National Institute for Health and Care Excellence (UK-NICE) and European Society of Cardiology (ESC) guidelines advise natriuretic peptide (NP) assessment in patients presenting to primary care with symptoms possibly due to chronic heart failure (HF), to determine need for specialist involvement. This prospective service evaluation aimed to describe the diagnostic and prognostic utility of these guidelines.
Figure 1 Short axis cine SSFP images in end-diastole, corresponding native T1 mapping, late gadol... more Figure 1 Short axis cine SSFP images in end-diastole, corresponding native T1 mapping, late gadolinium enhancement (LGE) images, ECV mapping and myocardial blood flow mapping in two patients with cardiac amyloidosis, the same mass, but different LGE patterns. Top: subendocardial LGE, high ECV values and borderline myocardial rest perfusion values. Bottom: transmural LGE, very high ECV values and reduced myocardial rest perfusion values.
Endocrinology, Diabetes & Metabolism Case Reports, Aug 1, 2013
Type 1 pseudohypoaldosteronism (PHA) is a rare heterogeneous group of disorders characterised by ... more Type 1 pseudohypoaldosteronism (PHA) is a rare heterogeneous group of disorders characterised by resistance to aldosterone action. There is resultant salt wasting in the neonatal period, with hyperkalaemia and metabolic acidosis. Only after results confirm isolated resistance to aldosterone can the diagnosis of type 1 PHA be confidently made. Type 1 PHA can be further classified into i) renal type 1 (autosomal dominant (AD)) and ii) multiple target organ defect/systemic type 1 (autosomal recessive (AR)). The aim of this case series was to characterise the mode of presentation, management and short-term clinical outcomes of patients with PHA type 1. Case notes of newly diagnosed infants presenting with PHA type 1 were reviewed over a 5-year time period. Seven patients were diagnosed with PHA type 1. Initial presentation ranged from 4 to 28 days of age. Six had weight loss as a presenting feature. All subjects had hyperkalaemia, hyponatraemia, with elevated renin and aldosterone levels. Five patients have renal PHA type 1 and two patients have systemic PHA type, of whom one has had genetic testing to confirm the AR gene mutation on the SCNN1A gene. Renal PHA type 1 responds well to salt supplementation, whereas management of patients with systemic PHA type 1 proves more difficult as they are likely to get frequent episodes of electrolyte imbalance requiring urgent correction. Learning points: †Patients with type 1 PHA are likely to present in the neonatal period with hyponatraemia, hyperkalaemia and metabolic acidosis and can be diagnosed by the significantly elevated plasma renin activity and aldosterone levels. †The differential diagnosis of type 1 PHA includes adrenal disorders such as adrenal hypoplasia and congenital adrenal hyperplasia; thus, adrenal function including cortisol levels, 17-hydroxyprogesterone and a urinary steroid profile are required. Secondary (transient) causes of PHA may be due to urinary tract infections or renal anomalies; thus, urine culture and renal ultrasound scan are required respectively. †A differentiation between renal and systemic PHA type 1 may be made based on sodium requirements, ease of management of electrolyte imbalance, sweat test results and genetic testing. †Management of renal PHA type 1 is with sodium supplementation, and requirements often decrease with age. †Systemic PHA type 1 requires aggressive and intensive fluid and electrolyte management. Securing an enteral feeding route and i.v. access are essential to facilitate ongoing therapy.
ORIGINAL PAPER The determinants of serum vitamin D levels in participants in a melanoma case–control study living in a temperate climate
Background We report the determinants of serum levels of vitamin D in a UK melanoma case–control ... more Background We report the determinants of serum levels of vitamin D in a UK melanoma case–control study ben-efitting from detailed exposure and genotyping data. Methods Sun exposure, supplemental vitamin D, and SNPs reported to be associated with serum levels were assessed as predictors of a single serum 25-hydroxyvitamin D3 measurement adjusted for season, age, sex, and body mass index. Results Adjusted analyses showed that vitamin D levels were sub-optimal especially in the sun-sensitive individu-als (-2.61 nmol/L, p = 0.03) and for inheritance of a genetic variant in the GC gene coding for the vitamin D-binding protein (-5.79 for heterozygotes versus wild type, p = \0.0001). Higher levels were associated with
Clinical practice guidelines (CPGs) relating to laboratory diagnostic testing are increasingly pr... more Clinical practice guidelines (CPGs) relating to laboratory diagnostic testing are increasingly produced with the aim of standardizing practice and improving patient care based on the best available evidence. However, the production of a CPG is merely the first step in the process of getting evidence into practice, to be undertaken by laboratories and other stakeholders. This process should evaluate the information provided in the guidelines on laboratory tests, devise a strategy for implementing the CPG or the laboratory aspects of the CPG and finally, once implemented, assess the impact of the CPG on clinical practice, patient outcomes and costs of care. The purpose of CPG evaluation by the laboratory is to determine whether sufficient information is provided on the particular test recommended. CPGs may not always be written with the involvement of a laboratory specialist and this underlies the paucity of relevant information in some national guidelines. When laboratory specialists...
Cumulative effects of growth hormone and insulin-like growth factor-1 exposure on cardiovascular, cerebrovascular and metabolic co-morbidities in acromegaly patients
046 Age–QRST angle score differentiates survival and predicts early and late mortality in 1843 ACS patients
Heart, 2010
Introduction Accurate and rapid risk assessment is central to the management of patients presenti... more Introduction Accurate and rapid risk assessment is central to the management of patients presenting with acute coronary syndromes (ACS). Simple data from the resting 12-lead electrocardiogram (ECG) is immediately available at first medical contact and may help predict mortality. Methods We regressed 30-day and 2-year mortality on simple ECG variables and clinical characteristics available during admission in 1843 patients with ACS in the EMMACE 2 cohort to generate a parsimonious model that was validated in 550 ACS patients from the EMMACE 1 cohort. The absolute difference between the frontal QRS and frontal T wave axis was calculated as (T wave axis – QRS axis) and if greater than 180 degrees was subtracted from 360, to give a continuous variable between 0 and 180 degrees. Association between mortality and potential predictor factors were quantified by ORs with 95% CIs. An age-QRST angle score was developed and its discriminative performance assessed using the C-statistic. Cox proportional hazards was used to generate survival models, and experiences analysed using Kaplan–Meier estimates. Results The mean (SD) age was 70.1 (13.1) years; and 1547 (61.9%) were male. Of the cohort 942 (37.7%) were non ST-elevation myocardial infarction (NSTEMI), 755 (30.2%) were STEMI and 802 (32.1%) were troponin negative ACS. After adjustment for age, heart failure, previous AMI, heart rate, systolic BP, ST depression, creatinine, elevated cardiac markers and inpatient PCI, the QRS-T angle carried the greatest significance of the ECG parameters. Age-QRST angle score powerfully discriminated 30-day and 2-year mortality (C statistic 0.74, 95% CI 0.71 to 0.78) and 2-year (C statistic 0.76, 95% CI 0.74 to 0.78) mortality, and maintained its performance in the EMMACE-1 validation cohort (C statistic 0.79, 95% CI 0.75 to 0.83) at 30-days and (C statistic 0.76, 95% CI 0.71 to 0.8) at 2-years. Significant differences in survival experience for 2 year survival were evident by age-QRST angle score (Score 0=3.7%, Score 1=14.4%, Score 2=30.2%, Score 3=38.2%, Score 4=57.3%) (Abstract 46 Figure 1). Conclusions Our results indicate that a wide frontal plane QRS-T angle is strongly predictive of mortality and long-term survival following ACS. The proposed model has several advantages over other risk scores in that it is parsimonious, objective (requiring no ECG interpretation) and rapidly available and thus truly near-point. Abstract 46 Figure 1 Survival Function at mean of covariates.
Lymphedema often responds to compression therapy which can also cause undesirable cardiac overloa... more Lymphedema often responds to compression therapy which can also cause undesirable cardiac overload if heart failure coexists. We hypothesized that the biomarker B-type natriuretic peptide (BNP) can be used to screen lymphedema patients for undetected cardiac dysfunction. We studied unselected consecutive patients with lymphedema to determine their BNP status and compared these data with those obtained from healthy subjects without known cardiovascular diseases. Out of a total of 305 subjects with lymphedema screened, 102 (33%) consented to take part in this study. The majority (87%) were female with a mean age of 60.5 +/- 13.2 (SD) years, and 47% had just lower limb swelling. The groups were equally divided between cancer and non-cancer related causes. There were 45 females and 4 males under 60 years old, and 44 female and 9 male patients over 60 years old. Median (IQR) BNP (ng/L) were as follows: <60 years females = 17.9 (15.2) (median [RR: 3 - 64] and males = 12.4 (14.7) [RR: 0...
The British journal of general practice : the journal of the Royal College of General Practitioners, 2005
Healthcare costs attributable to obesity have previously involved estimations based on costs of d... more Healthcare costs attributable to obesity have previously involved estimations based on costs of diseases commonly considered as having obesity as an underlying factor. To quantify the impact of obesity on total primary care drug prescribing. Review of computer generated and handwritten prescriptions to determine total prescribing volume for all drug classes. Twenty-three general practice surgeries in the UK. Stratified random selection of 1150 patients who were obese (body mass index [BMI]>30 kg/m(2)) and 1150 age and sex-matched controls of normal weight (BMI 18.5-<25 kg/m(2)). Retrospective review of medical records over an 18-month period. A higher percentage of patients who were obese, compared with those of normal weight, were prescribed at least one drug in the following disease categories: cardiovascular (36% versus 20%), central nervous system (46% versus 35%), endocrine (26% versus 18%), and musculoskeletal and joint disease (30% versus 22%). All of these categories h...
Development of acromegaly during treatment of hyperprolactinemia with bromocriptine: an unusual acidophil stem cell adenoma
The Journal of Clinical Endocrinology & Metabolism, 1996
We present clinical details of a patient with a 20-yr history of amennorhea, a pituitary tumor, e... more We present clinical details of a patient with a 20-yr history of amennorhea, a pituitary tumor, elevated PRL levels, and initially undetectable GH. Bromocriptine failed to fully suppress PRL, and there was no tumor shrinkage. Within 7 months of starting bromocriptine treatment, the patient developed clinical and biochemical signs of acromegaly. At surgery, a stem cell adenoma was excised. The mechanisms by which bromocriptine may have resulted in the development of acromegaly in this patient are discussed.
The ageing population is expected to increase the burden of osteoporosis on the health care syste... more The ageing population is expected to increase the burden of osteoporosis on the health care system. Secondary causes of osteoporosis are found in a proportion of patients. There is much controversy regarding the best work-up for patients who have been diagnosed as having osteoporosis based on bone mineral density. It is difficult to decide where interventions should be targeted both from a patient's perspective and for cost effectiveness. We evaluated the utility of a standard panel (full blood count, plasma viscosity, plasma protein, electrophoresis, urine Bence Jones protein, thyroid function test, bone profile, fasting lipids and liver function test) of biochemical investigations in 327 consecutive patients (287 females, 40 males) referred to the new patient osteoporosis clinic from April 1999 to March 2000. Patients were characterised after measurement of spinal/femoral neck bone mineral density after a dual energy X-ray absorptiometry (DEXA) scan. There were 88 patients with osteoporosis, 91 with osteopenia, 130 had normal bone mineral density and 20 who did not have a bone scan. No case of multiple myeloma was found in this cohort of patients. There was no difference in the mean plasma viscosity of patients with and without osteoporosis (P=0.182). There was no significant difference in the abnormal urine calcium/creatinine (Ca/Cr ratio) in patients with osteoporosis and those without osteoporosis (P=0.316). There was no significant difference in the prevalence of hypothyroidism (P=0.213) or thyrotoxicosis (P=0.138) in patients with and without osteoporosis. There was no strong correlation between cholesterol concentrations and osteoporosis (r=0.069). We found no utility in performing a myeloma screen. A small proportion of patients had abnormalities of calcium homeostasis or thyroid disease. We recommend that a screening biochemical evaluation should be restricted to calcium/bone profile and thyroid function tests in patients with a presumptive diagnosis of osteoporosis.
antigen measurements, thus increasing costs substantially. It may be that this cost would be just... more antigen measurements, thus increasing costs substantially. It may be that this cost would be justifiable if the result was a reinvigoration of flagging sexual appetites, physical strength and general wellbeing of an ageing male population, as they face more years in the workforce before retirement. For now the case is far from proven. Adopting a single cutoff for reporting serum testosterone in males, irrespective of age, may contribute substantially to the widespread use of an expensive treatment with unproven safety and efficacy. We believe that biochemistry departments should report age-related reference intervals for total and (calculated) free testosterone, thus enabling identification of individuals with significant testosterone deficiency who are likely to benefit from replacement therapy.
The term 'big data' is used to refer both to data-sets and to how the data are analysed and used.... more The term 'big data' is used to refer both to data-sets and to how the data are analysed and used. The data may be heterogeneous and complex and may change or accumulate rapidly. A given data-set may combine many different databases, so connecting them together can present a big challenge.
Background: We aimed to investigate in patients with type 2 diabetes whether aortic stiffness is:... more Background: We aimed to investigate in patients with type 2 diabetes whether aortic stiffness is: (i) associated with glycaemic control, (ii) associated with adverse outcomes and (iii) can be reversed on treatment with RAAS inhibition. Methods: Patients with type 2 diabetes (N = 94) and low vascular risk underwent assessment of cardiovascular risk and CMR assessment of ascending aortic distensibility (AAD), descending aortic distensibility (DAD) and aortic pulse wave velocity (PWV). Of these patients a subgroup with recent onset microalbuminuria (N = 25) were treated with renin-angiotensin-aldosterone system (RAAS) inhibition and imaging repeated after 1 year. All 94 patients were followed up for 2.4 years for major adverse cardiovascular disease (CVD) events including myocardial infarction detected on late gadolinium enhancement CMR. Results: Ascending aortic distensibility, DAD and PWV all had a significant association with age and 24 h systolic blood pressure but only AAD had a significant association with glycaemic control, measured as HbA1c (Beta − 0.016, P = 0.04). The association between HbA1c and AAD persisted even after correction for age and hypertension. CVD events occurred in 19/94 patients. AAD, but not DAD or PWV, was associated with CVD events (hazard ratio 0.49, 95% confidence interval 0.25-0.95, P = 0.01). On treatment with RAAS inhibition, AAD, but not DAD or PWV, showed significant improvement from 1.51 ± 1.15 to 1.97 ± 1.07 10 −3 mmHg −1 , P = 0.007. Conclusions: Ascending aortic distensibility measured by CMR is independently associated with poor glycaemic control and adverse cardiovascular events. Furthermore it may be reversible on treatment with RAAS inhibition. AAD is a promising marker of cardiovascular risk in asymptomatic patients with type 2 diabetes and has potential use as a surrogate cardiovascular endpoint in studies of novel hypoglycaemic agents.
Immunoassay methods for prolactin detect macroprolactin (i.e. high molecular mass complexes of pr... more Immunoassay methods for prolactin detect macroprolactin (i.e. high molecular mass complexes of prolactin) to various degrees. Therefore it is generally assumed that the widely differing results by methods that measure both moieties to a differing extent are due to the presence of macroprolactin. We present a case which challenges such an assumption and suggest that precipitation by polyethylene glycol is the most reliable screen for identifying macroprolactin (and/or interfering antibodies if present).
The reference intervals (RIs) given in laboratory reports have an important role in aiding clinic... more The reference intervals (RIs) given in laboratory reports have an important role in aiding clinicians in interpreting test results in reference to values of healthy populations. In this report, we present a proposed protocol and standard operating procedures (SOPs) for common use in conducting multicenter RI studies on a national or international scale. The protocols and consensus on their contents were refined through discussions in recent C-RIDL meetings. The protocol describes in detail (1) the scheme and organization of the study, (2) the target population, inclusion/ exclusion criteria, ethnicity, and sample size, (3) health status questionnaire, (4) target analytes, (5) blood collection, (6) sample processing and storage, (7) assays, (8) cross-check testing, (9) ethics, (10) data analyses, and (11) reporting of results. In addition, the protocol proposes the common measurement of a panel of sera when no standard materials exist for harmonization of test results. It also describes the requirements of the central laboratory, including the method of cross-check testing between the central laboratory of each country and local laboratories. This protocol and the SOPs remain largely exploratory and may require a reevaluation from the practical point of view after their implementation in the ongoing worldwide study. The paper is mainly intended to be a basis for discussion in the scientific community.
European Heart Journal - Quality of Care and Clinical Outcomes, Nov 19, 2018
The UK National Institute for Health and Care Excellence (UK-NICE) and European Society of Cardio... more The UK National Institute for Health and Care Excellence (UK-NICE) and European Society of Cardiology (ESC) guidelines advise natriuretic peptide (NP) assessment in patients presenting to primary care with symptoms possibly due to chronic heart failure (HF), to determine need for specialist involvement. This prospective service evaluation aimed to describe the diagnostic and prognostic utility of these guidelines.
Figure 1 Short axis cine SSFP images in end-diastole, corresponding native T1 mapping, late gadol... more Figure 1 Short axis cine SSFP images in end-diastole, corresponding native T1 mapping, late gadolinium enhancement (LGE) images, ECV mapping and myocardial blood flow mapping in two patients with cardiac amyloidosis, the same mass, but different LGE patterns. Top: subendocardial LGE, high ECV values and borderline myocardial rest perfusion values. Bottom: transmural LGE, very high ECV values and reduced myocardial rest perfusion values.
Endocrinology, Diabetes & Metabolism Case Reports, Aug 1, 2013
Type 1 pseudohypoaldosteronism (PHA) is a rare heterogeneous group of disorders characterised by ... more Type 1 pseudohypoaldosteronism (PHA) is a rare heterogeneous group of disorders characterised by resistance to aldosterone action. There is resultant salt wasting in the neonatal period, with hyperkalaemia and metabolic acidosis. Only after results confirm isolated resistance to aldosterone can the diagnosis of type 1 PHA be confidently made. Type 1 PHA can be further classified into i) renal type 1 (autosomal dominant (AD)) and ii) multiple target organ defect/systemic type 1 (autosomal recessive (AR)). The aim of this case series was to characterise the mode of presentation, management and short-term clinical outcomes of patients with PHA type 1. Case notes of newly diagnosed infants presenting with PHA type 1 were reviewed over a 5-year time period. Seven patients were diagnosed with PHA type 1. Initial presentation ranged from 4 to 28 days of age. Six had weight loss as a presenting feature. All subjects had hyperkalaemia, hyponatraemia, with elevated renin and aldosterone levels. Five patients have renal PHA type 1 and two patients have systemic PHA type, of whom one has had genetic testing to confirm the AR gene mutation on the SCNN1A gene. Renal PHA type 1 responds well to salt supplementation, whereas management of patients with systemic PHA type 1 proves more difficult as they are likely to get frequent episodes of electrolyte imbalance requiring urgent correction. Learning points: †Patients with type 1 PHA are likely to present in the neonatal period with hyponatraemia, hyperkalaemia and metabolic acidosis and can be diagnosed by the significantly elevated plasma renin activity and aldosterone levels. †The differential diagnosis of type 1 PHA includes adrenal disorders such as adrenal hypoplasia and congenital adrenal hyperplasia; thus, adrenal function including cortisol levels, 17-hydroxyprogesterone and a urinary steroid profile are required. Secondary (transient) causes of PHA may be due to urinary tract infections or renal anomalies; thus, urine culture and renal ultrasound scan are required respectively. †A differentiation between renal and systemic PHA type 1 may be made based on sodium requirements, ease of management of electrolyte imbalance, sweat test results and genetic testing. †Management of renal PHA type 1 is with sodium supplementation, and requirements often decrease with age. †Systemic PHA type 1 requires aggressive and intensive fluid and electrolyte management. Securing an enteral feeding route and i.v. access are essential to facilitate ongoing therapy.
ORIGINAL PAPER The determinants of serum vitamin D levels in participants in a melanoma case–control study living in a temperate climate
Background We report the determinants of serum levels of vitamin D in a UK melanoma case–control ... more Background We report the determinants of serum levels of vitamin D in a UK melanoma case–control study ben-efitting from detailed exposure and genotyping data. Methods Sun exposure, supplemental vitamin D, and SNPs reported to be associated with serum levels were assessed as predictors of a single serum 25-hydroxyvitamin D3 measurement adjusted for season, age, sex, and body mass index. Results Adjusted analyses showed that vitamin D levels were sub-optimal especially in the sun-sensitive individu-als (-2.61 nmol/L, p = 0.03) and for inheritance of a genetic variant in the GC gene coding for the vitamin D-binding protein (-5.79 for heterozygotes versus wild type, p = \0.0001). Higher levels were associated with
Clinical practice guidelines (CPGs) relating to laboratory diagnostic testing are increasingly pr... more Clinical practice guidelines (CPGs) relating to laboratory diagnostic testing are increasingly produced with the aim of standardizing practice and improving patient care based on the best available evidence. However, the production of a CPG is merely the first step in the process of getting evidence into practice, to be undertaken by laboratories and other stakeholders. This process should evaluate the information provided in the guidelines on laboratory tests, devise a strategy for implementing the CPG or the laboratory aspects of the CPG and finally, once implemented, assess the impact of the CPG on clinical practice, patient outcomes and costs of care. The purpose of CPG evaluation by the laboratory is to determine whether sufficient information is provided on the particular test recommended. CPGs may not always be written with the involvement of a laboratory specialist and this underlies the paucity of relevant information in some national guidelines. When laboratory specialists...
Cumulative effects of growth hormone and insulin-like growth factor-1 exposure on cardiovascular, cerebrovascular and metabolic co-morbidities in acromegaly patients
046 Age–QRST angle score differentiates survival and predicts early and late mortality in 1843 ACS patients
Heart, 2010
Introduction Accurate and rapid risk assessment is central to the management of patients presenti... more Introduction Accurate and rapid risk assessment is central to the management of patients presenting with acute coronary syndromes (ACS). Simple data from the resting 12-lead electrocardiogram (ECG) is immediately available at first medical contact and may help predict mortality. Methods We regressed 30-day and 2-year mortality on simple ECG variables and clinical characteristics available during admission in 1843 patients with ACS in the EMMACE 2 cohort to generate a parsimonious model that was validated in 550 ACS patients from the EMMACE 1 cohort. The absolute difference between the frontal QRS and frontal T wave axis was calculated as (T wave axis – QRS axis) and if greater than 180 degrees was subtracted from 360, to give a continuous variable between 0 and 180 degrees. Association between mortality and potential predictor factors were quantified by ORs with 95% CIs. An age-QRST angle score was developed and its discriminative performance assessed using the C-statistic. Cox proportional hazards was used to generate survival models, and experiences analysed using Kaplan–Meier estimates. Results The mean (SD) age was 70.1 (13.1) years; and 1547 (61.9%) were male. Of the cohort 942 (37.7%) were non ST-elevation myocardial infarction (NSTEMI), 755 (30.2%) were STEMI and 802 (32.1%) were troponin negative ACS. After adjustment for age, heart failure, previous AMI, heart rate, systolic BP, ST depression, creatinine, elevated cardiac markers and inpatient PCI, the QRS-T angle carried the greatest significance of the ECG parameters. Age-QRST angle score powerfully discriminated 30-day and 2-year mortality (C statistic 0.74, 95% CI 0.71 to 0.78) and 2-year (C statistic 0.76, 95% CI 0.74 to 0.78) mortality, and maintained its performance in the EMMACE-1 validation cohort (C statistic 0.79, 95% CI 0.75 to 0.83) at 30-days and (C statistic 0.76, 95% CI 0.71 to 0.8) at 2-years. Significant differences in survival experience for 2 year survival were evident by age-QRST angle score (Score 0=3.7%, Score 1=14.4%, Score 2=30.2%, Score 3=38.2%, Score 4=57.3%) (Abstract 46 Figure 1). Conclusions Our results indicate that a wide frontal plane QRS-T angle is strongly predictive of mortality and long-term survival following ACS. The proposed model has several advantages over other risk scores in that it is parsimonious, objective (requiring no ECG interpretation) and rapidly available and thus truly near-point. Abstract 46 Figure 1 Survival Function at mean of covariates.
Lymphedema often responds to compression therapy which can also cause undesirable cardiac overloa... more Lymphedema often responds to compression therapy which can also cause undesirable cardiac overload if heart failure coexists. We hypothesized that the biomarker B-type natriuretic peptide (BNP) can be used to screen lymphedema patients for undetected cardiac dysfunction. We studied unselected consecutive patients with lymphedema to determine their BNP status and compared these data with those obtained from healthy subjects without known cardiovascular diseases. Out of a total of 305 subjects with lymphedema screened, 102 (33%) consented to take part in this study. The majority (87%) were female with a mean age of 60.5 +/- 13.2 (SD) years, and 47% had just lower limb swelling. The groups were equally divided between cancer and non-cancer related causes. There were 45 females and 4 males under 60 years old, and 44 female and 9 male patients over 60 years old. Median (IQR) BNP (ng/L) were as follows: <60 years females = 17.9 (15.2) (median [RR: 3 - 64] and males = 12.4 (14.7) [RR: 0...
The British journal of general practice : the journal of the Royal College of General Practitioners, 2005
Healthcare costs attributable to obesity have previously involved estimations based on costs of d... more Healthcare costs attributable to obesity have previously involved estimations based on costs of diseases commonly considered as having obesity as an underlying factor. To quantify the impact of obesity on total primary care drug prescribing. Review of computer generated and handwritten prescriptions to determine total prescribing volume for all drug classes. Twenty-three general practice surgeries in the UK. Stratified random selection of 1150 patients who were obese (body mass index [BMI]>30 kg/m(2)) and 1150 age and sex-matched controls of normal weight (BMI 18.5-<25 kg/m(2)). Retrospective review of medical records over an 18-month period. A higher percentage of patients who were obese, compared with those of normal weight, were prescribed at least one drug in the following disease categories: cardiovascular (36% versus 20%), central nervous system (46% versus 35%), endocrine (26% versus 18%), and musculoskeletal and joint disease (30% versus 22%). All of these categories h...
Development of acromegaly during treatment of hyperprolactinemia with bromocriptine: an unusual acidophil stem cell adenoma
The Journal of Clinical Endocrinology & Metabolism, 1996
We present clinical details of a patient with a 20-yr history of amennorhea, a pituitary tumor, e... more We present clinical details of a patient with a 20-yr history of amennorhea, a pituitary tumor, elevated PRL levels, and initially undetectable GH. Bromocriptine failed to fully suppress PRL, and there was no tumor shrinkage. Within 7 months of starting bromocriptine treatment, the patient developed clinical and biochemical signs of acromegaly. At surgery, a stem cell adenoma was excised. The mechanisms by which bromocriptine may have resulted in the development of acromegaly in this patient are discussed.
The ageing population is expected to increase the burden of osteoporosis on the health care syste... more The ageing population is expected to increase the burden of osteoporosis on the health care system. Secondary causes of osteoporosis are found in a proportion of patients. There is much controversy regarding the best work-up for patients who have been diagnosed as having osteoporosis based on bone mineral density. It is difficult to decide where interventions should be targeted both from a patient's perspective and for cost effectiveness. We evaluated the utility of a standard panel (full blood count, plasma viscosity, plasma protein, electrophoresis, urine Bence Jones protein, thyroid function test, bone profile, fasting lipids and liver function test) of biochemical investigations in 327 consecutive patients (287 females, 40 males) referred to the new patient osteoporosis clinic from April 1999 to March 2000. Patients were characterised after measurement of spinal/femoral neck bone mineral density after a dual energy X-ray absorptiometry (DEXA) scan. There were 88 patients with osteoporosis, 91 with osteopenia, 130 had normal bone mineral density and 20 who did not have a bone scan. No case of multiple myeloma was found in this cohort of patients. There was no difference in the mean plasma viscosity of patients with and without osteoporosis (P=0.182). There was no significant difference in the abnormal urine calcium/creatinine (Ca/Cr ratio) in patients with osteoporosis and those without osteoporosis (P=0.316). There was no significant difference in the prevalence of hypothyroidism (P=0.213) or thyrotoxicosis (P=0.138) in patients with and without osteoporosis. There was no strong correlation between cholesterol concentrations and osteoporosis (r=0.069). We found no utility in performing a myeloma screen. A small proportion of patients had abnormalities of calcium homeostasis or thyroid disease. We recommend that a screening biochemical evaluation should be restricted to calcium/bone profile and thyroid function tests in patients with a presumptive diagnosis of osteoporosis.
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Papers by julian barth