Anti-Müllerian hormone reflects the severity of polycystic ovary syndrome.

OBJECTIVE: To examine the relationship between anti-Müllerian hormone (AMH) and the severity of the phenotype of patients with polycystic ovary syndrome (PCOS) and whether AMH can act as a diagnostic marker for PCOS? DESIGN: A prospective diagnostic utility study of AMH as a marker of PCOS. PATIENTS: A consecutive series of women presenting to a tertiary infertility clinic (n = 164) plus a second series of women prepared for assisted conception treatments (n = 89) recruited between June 2012 and May 2013. MEASUREMENTS: Polycystic ovary syndrome was diagnosed using the Rotterdam criteria. AMH was measured using the Generation II assay (Beckman Coulter). The diagnostic utility of AMH was established using receiver operator characteristic (ROC) curves. Cut-off values for the individual features of PCOS are proposed. RESULTS: There was a significant difference in serum AMH concentration in women with normal ovaries (13·2 pmol/l), polycystic ovary morphology (PCOM) alone (37·8 pmol/l) and PCOS (53·2 pmol/l). Follicle number, increasing cycle length and evidence of hyperandrogenism were all independently associated with serum AMH concentration (P < 0·01). AMH was significantly affected by the different phenotypic presentations of PCOS with those with all components (PCOM, HA and OA) having the highest mean value [72·7 pmol/l (P < 0·01)]. CONCLUSIONS: Serum AMH has the capacity to act as a diagnostic test for PCOS. Moreover, since its value rises with the more marked phenotypes, different cut-off values need to be used to differentiate those patients with polycystic ovarian morphology (PCOM), hyperandrogenism (HA) and oligoanovulation (OA).

A short course of metformin does not reduce OHSS in a GnRH antagonist cycle for women with PCOS undergoing IVF: a randomised placebo-controlled trial.

STUDY QUESTION: Does 'metformin' reduce the incidence of ovarian hyperstimulation syndrome (OHSS) for women with polycystic ovary syndrome (PCOS) undergoing a GnRH antagonist assisted conception treatment cycle? SUMMARY ANSWER: A short course of metformin does not reduce the incidence of OHSS for women with PCOS undergoing a GnRH antagonist treatment cycle. WHAT IS KNOWN ALREADY: Metformin does reduce the incidence of OHSS in a GnRH-agonist treatment cycle. STUDY DESIGN, SIZE, DURATION: A randomised placebo-controlled trial (RCT) using metformin or placebo. Randomisation was blinded to both patient and investigator, using a random permuted blocks method with a 50:50 allocation ratio. The study was completed over 5 years (2009-2014) with 153 randomised patients. A sample size calculation based on the incidence of OHSS was completed prospectively suggesting a minimum of 146 recruits was required for the trial with a power of 80% and a type 1 error of 0.05. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients met the Rotterdam criteria for PCOS and were treated with a standard GnRH antagonist IVF/ICSI treatment cycle in a tertiary infertility clinic. The study medication was started prior to stimulation and continued to oocyte retrieval. Of the 153 patients, 77 received metformin and 76 placebo. MAIN RESULTS AND THE ROLE OF CHANCE: There was no reduction in the incidence of moderate-severe OHSS (Placebo (PLA) 12.2%, metformin (MET) = 16%, 95% CI -0.08-0.16, P = 0.66). There was no difference in total gonadotrophin dose (PLA = 1200, MET = 1200, 95% CI -118.67-118.67, P = 0.75), oocytes retrieved (PLA = 15, MET = 14, 95% CI -2.37-4.37, P = 0.66) or fertilisation rate (PLA = 60.7%, MET = 53.3%, 95% CI -0.96-14.94, P = 0.07). However, using metformin resulted in a reduced clinical pregnancy rate (CPR) per cycle started (PLA = 48.7%, MET = 28.6%, 95% CI 0.04-0.35, P = 0.02) and live birth rate (PLA = 51.6%, MET = 27.6%, 95% CI 0.05-0.40, P = 0.02). Furthermore, when ethnicity was taken into account there was a significant reduction in pregnancy outcome for the South Asian population irrespective of metformin or placebo use (CPR per cycle started, White Caucasian = 44.4%, South Asian = 19.4%; 95% CI 0.06-0.39, P = 0.01). LIMITATIONS, REASONS FOR CAUTION: This study was only undertaken on an infertility population with PCOS with a limited duration of study medication use. WIDER IMPLICATIONS OF THE FINDINGS: This is the first adequately powered RCT to assess the impact of metformin on OHSS in a high-risk group (women with PCOS) undergoing a GnRH antagonist cycle. It does not support the empirical prescribing of metformin as an adjunct to a GnRH antagonist treatment cycle. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: EudraCT number 2009-010952-81. TRIAL REGISTRATION DATE: 21 September 2009. DATE OF FIRST PATIENT'S ENROLMENT: 30 October 2009.

The effect of metformin treatment in vivo on acute and long-term energy metabolism and progesterone production in vitro by granulosa cells from women with polycystic ovary syndrome.

STUDY QUESTION: What are the consequences of polycystic ovary syndrome (PCOS) pathology and metformin-pretreatment in vivo in women with PCOS on the metabolism and steroid production of follicular phenotype- and long-term cultured-granulosa cells (GC)? SUMMARY ANSWER: PCOS pathology significantly compromised glucose metabolism and the progesterone synthetic capacity of follicular- and long-term cultured-GCs and the metabolic impact of PCOS on GC function was alleviated by metformin-pretreatment in vivo. WHAT IS KNOWN ALREADY: Granulosa cells from women with PCOS have been shown to have an impaired insulin-stimulated glucose uptake and lactate production in vitro. However, these results were obtained by placing GCs in unphysiological conditions in culture medium containing high glucose and insulin concentrations. Moreover, existing data on insulin-responsive steroid production in vitro by PCOS GCs vary. STUDY DESIGN, SIZE AND DURATION: Case-control experimental research comparing glucose uptake, pyruvate and lactate production and progesterone production in vitro by GCs from three aetiological groups, all undergoing IVF; healthy control women (Control, n = 12), women with PCOS treated with metformin in vivo (Metformin, n = 8) and women with PCOS not exposed to metformin (PCOS, n = 8). The study was conducted over a period of 3 years between 2007 and 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Rotterdam criteria were used for the diagnosis of PCOS; all subjects were matched for age, BMI and baseline FSH. Individual patient cultures were undertaken with cells incubated in a validated, physiological, serum-free culture medium containing doses of 0-6 mM glucose and 0-100 ng/ml insulin for 6 h and 144 h to quantify the impact of treatments on acute and long-term metabolism, respectively, and progesterone production. The metabolite content of spent media was measured using spectrophotometric plate reader assay. The progesterone content of spent media was measured by enzyme-linked immunosorbent assay. Viable GC number was quantified after 144 h of culture by the vital dye Neutral Red uptake assay. MAIN RESULTS AND THE ROLE OF CHANCE: Granulosa cells from women with PCOS pathology revealed reduced pyruvate production and preferential lactate production in addition to their reduced glucose uptake during cultures (P < 0.05). Metformin pretreatment alleviated this metabolic lesion (P < 0.05) and enhanced cell proliferation in vitro (P < 0.05), but cells retained a significantly reduced capacity for progesterone synthesis compared with controls (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Although significant treatment effects were detected in this small cohort, further studies are required to underpin the molecular mechanisms of the effect of metformin on GCs. WIDER IMPLICATIONS OF THE FINDINGS: The individual patient culture strategy combined with multifactorial experimental design strengthens the biological interpretation of the data. Collectively, these results support the notion that there is an inherent impairment in progesterone biosynthetic capacity of the GCs from women with PCOS. The positive, acute metabolic effect and the negative long-term steroidogenic effect on GCs following metformin exposure in vivo may have important implications for follicular development and luteinized GC function when the drug is used in clinical practice. STUDY FUNDING/COMPETING INTERESTS: No competing interests. This work was supported by the UK Medical Research Council Grant Reference number G0800250.

Cardiovascular risk in patients with small and medium abdominal aortic aneurysms, and no history of cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is the main cause of death in people with abdominal aortic aneurysm (AAA). There is little evidence that screening for AAA reduces all-cause or cardiovascular mortality. The aim of the study was to assess whether subjects with a small or medium AAA (3·0-5·4 cm), without previous history of clinical CVD, had raised levels of CVD biomarkers or increased total mortality. METHODS: This prospective study included subjects with a small or medium AAA and controls, all without a history of clinical CVD. CVD biomarkers (high-sensitivity C-reactive protein, hs-CRP; heart-type fatty acid-binding protein, H-FABP) were measured, and survival was recorded. RESULTS: Of a total of 815 people, 476 with an AAA and 339 controls, a cohort of 86 with small or medium AAA (3-5·4 cm) and 158 controls, all with no clinical history of CVD, were identified. The groups were matched for age and sex. The AAA group had higher median (i.q.r.) levels of hs-CRP (2·8 (1·2-6·0) versus 1·3 (0·5-3·5) mg/l; P < 0·001) and H-FABP (4·6 (3·5-6·0) versus 4·0 (3·3-5·1) µg/l; P = 0·011) than controls. Smoking was more common in the AAA group; however, hs-CRP and H-FABP levels were not related to smoking. Mean survival was lower in the AAA group: 6·3 (95 per cent confidence interval (c·i.) 5·6 to 6·9) years versus 8·0 (7·6 to 8·1) years in controls (P < 0·001). Adjusted mortality was higher in the AAA group (hazard ratio 3·41, 95 per cent c·i. 2·11 to 9·19; P < 0·001). CONCLUSION: People with small or medium AAA and no clinical symptoms of CVD have higher levels of hs-CRP and H-FABP, and higher mortality compared with controls. They should continue to receive secondary prevention against CVD.

Acute intermittent porphyria: fatal complications of treatment.

Acute neurovisceral attacks of porphyria can be life threatening. They are rare and notoriously difficult to diagnose clinically, but should be considered, particularly in female patients with unexplained abdominal pain, and associated neurological or psychiatric features or hyponatraemia. The diagnosis might be suggested by altered urine colour and can be confirmed by finding an elevated porphobilinogen concentration in fresh urine protected from light. Severe attacks require treatment with intravenous haem arginate and supportive management with safe drugs, including adequate analgesia. Intravenous glucose in water solutions are contraindicated as they aggravate hyponatraemia, which can prove fatal.

B-type natriuretic peptide in lymphedema.

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: 0.2 - 44], >60 years females = 35.8 (57.9) [RR: 2 -247)] and males = 47.2 (44.1) [RR: 2 - 238]. For this population, the BNP concentration 100 ng/L was adopted as the value to exclude heart failure. Using this definition, 7 lymphedema subjects had BNP concentrations of 120 (19.8) ng/L, and all were found to have cardiac abnormalities on echocardiography. This study demonstrated that 93% of unselected subjects with lymphedema had BNP concentrations that exclude a diagnosis of heart failure. Those subjects with elevated BNP were found on subsequent echocardiography to have cardiac abnormalities. The use of a BNP assay is of potential value in screening patients who are more likely to have cardiac failure. Indicative factors include bilateral leg swelling, over the age of 50 years, breathlessness, where there is no known cause for the swelling. A BNP assay using a BNP concentration threshold of 100 ng/L (29 pmol/L) will identify those patients who require more detailed investigations.

Evaluation of the MP Rapid 2019-NCOV IgM/IgG combo POCT test vs. an established platform-based method.

BACKGROUND: Accurate and rapid testing for SARS-COV-2 antibodies could improve the diagnosis and management of COVID-19. In this study, we aim to evaluate the diagnostic accuracy of a commercially available point-of-care lateral flow kit independently and in comparison to an established platform-based system. METHOD: Samples from 144 PCR-confirmed COVID-19 cases and 130 pre-pandemic negative controls were tested in parallel by MP Rapid 2019-NCOV IgM/IgG Combo test and Roche Elecsys. Comparison of results based on serum and capillary blood testing was undertaken. RESULTS: Sensitivity at day 15 onwards was 100% for both methods. Between days 1 and 7 post admission, the IgM/IgG Combo test and Roche Elecsys shown sensitivity of 74% (95%CI: 62%-85%) vs. 67% (95% CI: 55%-79%, P = 0.3947). Combo test specificities were 100% for IgG, 98.5% for IgM vs. Roche Elecsys specificity of 100%. Concordance analysis showed 98.5% agreement to the Roche Elecsys method (Cohen's Kappa 0.96 95% CI [0.92-0.99]). Capillary blood results showed complete agreement with serum samples using the Combo test. CONCLUSION: In comparison to Roche Elecsys, our data show that the MP Rapid 2019-NCOV IgM/IgG Combo test provides a high-confidence assay system for the detection of previous exposure to SARS-COV-2 infection with advantage of affording near-patient testing.

The impact of the analytical performance specifications of calcium and albumin on adjusted calcium.

AIM: The generation of accurate, comparable results from traceable measurement procedures is a primary goal in harmonization efforts. In this study, the analytical performance of routine methods for calcium and albumin measurement is assessed to define the impact of the analytical bias of calcium and albumin on adjusted calcium equation performance and on reference intervals. METHOD: In collaboration with the Wales External Quality Assurance Scheme, six months' worth of anonymized data that cover a concentration range of clinical interest were collected. The data were grouped by analytical platforms/methods. RESULTS: Albumin BCG methods are positively biased (8%) to BCP methods. The overall bias for BCP methods ranges from 5.1 to -4.3% and the overall bias for BCG methods is from 2 to -6.7%. Bias for both methods is higher than the allowable minimal bias for albumin. Calcium concentrations for Roche Cobas CPC and NM-BAPTA, Beckman Arsenazo III, Abbott Architect Arsenazo III were within bias of 1.5 to -1%. However, Siemens calcium methods CPC and Arsenazo III appear to suffer from concentration-dependent bias ranging from +3 to -6%, which exceeds even the minimal allowable limits for calcium (1.3%). Adjusted calcium shows significant bias of 11%. Even with the exclusion of Siemens Advia, the scatter of adjusted calcium results exceeds that for total calcium. CONCLUSION: This study shows wider than acceptable analytical variation for albumin and calcium. This variation may contribute to overall adjusted calcium equations variation and invalidate the application of a harmonized reference interval for calcium and albumin.

Prospective study comparing the outcome of a population-specific adjusted calcium equation to ionized calcium.

BACKGROUND: Calcium circulates bound to albumin and changes in albumin concentration will therefore affect total calcium measurements. In order to mitigate this, correction factors are frequently used. The most widely used correction equation was described by Payne and colleagues in 1973. This equation was derived from well-defined hospitalized patients' data. Current clinical practice is consistent with the general application of the adjusted calcium equation irrespective of clinical setting. This study aims to assess the validity of this approach by the derivation of a community care-specific adjusted calcium equation ('community equation') and the comparison of its performance to a hospitalized patient equation and ionized calcium. METHOD: Retrospective data were collected according to Payne's criteria from an inpatient and community care setting. Data were used to derive the two equations: the in-patient equation and community equation. The outcome of these equations was compared with ionized calcium obtained from 123 healthy participants. RESULTS: The community equation correctly identified the calcium status of 92% of the 123 healthy participants, while the inpatient equation identified 46% only. Regression analysis against ionized calcium showed a higher R2 for the community equation than for the inpatient equation. Furthermore, we have shown that mean albumin and calcium concentrations are significantly different between these two populations. CONCLUSION: In this study, we found that the diagnostic accuracy of the adjusted calcium equation in ambulant patients was improved by the derivation of a population-specific equation for the community care setting.

The effect of different analytical platforms and methods on the performance of population-specific adjusted calcium equation.

BACKGROUND: A recent attempt to improve the diagnostic value of adjusted calcium addressed a primary care-specific adjusted calcium equation, but validated the new equation for Roche Cobas, BCG and NM-BAPTA methods only. In this study, we aim to validate a population-specific equation for other methods and platforms. METHOD: We collected retrospective patient data-sets from 15 hospital laboratories using a range of commercially available analytical platforms and methods for calcium and albumin measurements. Raw data-sets were collected and filtered according to Payne's criteria, and separate adjusted calcium equations were derived for hospitalized and primary care patients. RESULTS: Mean albumin and calcium results were significantly higher in primary care populations (P < 0.0001). The prevalence of hypocalcaemia using adjusted calcium ranged between 6% and 44% for inpatient data-sets and was higher in users of BCG methods. The application of community-specific adjustment equation to primary care data-sets reduced the prevalence of hypocalcaemia (mean 1.7%, range 0.8-3.7%). CONCLUSION: We demonstrated that the use of a community-specific calcium adjustment equation to a primary care population reduces both the percentage and the variation of hypocalcaemia between different laboratories.

Albumin and calcium reference interval using healthy individuals and a data-mining approach.

BACKGROUND: Harmonization of reference intervals for analytes that have a sound calibration and metrological traceability is a widely recommended practice. The UK Pathology Harmony has recently harmonized reference intervals for calcium and albumin. In this study, we have determined the reference intervals for calcium and albumin on the UK's most commonly used analytical platforms. METHOD: A prospective reference population of healthy individuals was recruited according to the IFCC CRIDL criteria. A second indirect population was collected from 14 primary care setting and measured in laboratories using various analytical platforms and methods (Roche, Abbott, Beckman and Siemens analytical platforms). RESULTS: In total, 299 subjects were recruited; the central 95th centile values for calcium for three out of four analytical platforms were in a close agreement with UK Pathology Harmony reference intervals of 2.2-2.6 mmol/L. Reference intervals of BCG methods from both cohorts and irrespective of analytical platforms were higher for both lower and upper reference limits than those for BCP. In comparison, the indirect study showed an age-related variation. The younger population reference intervals varied by up to 5.7% at the lower reference limit and up to 12% at the upper reference limit compared with Pathology Harmony reference intervals, and the older population showed a variation of up to 14% at both limits. CONCLUSION: While calcium reference intervals can be a subject for harmonization, albumin reference intervals studied showed large variation which is unsupportive of embracing a common reference interval for albumin.

Jugular venous neurone specific enolase (NSE) increases following carotid endarterectomy under general, but not local, anaesthesia.

INTRODUCTION: Previous studies indicate that local (LA) rather than general anaesthesia (GA) for carotid endarterectomy (CEA) is associated with reflex hypertension and preservation of cerebral cytochrome oxidase after carotid clamping. The hypothesis that LA offers protection against ischaemic cerebral injury has been investigated by measuring ipsilateral jugular venous neurone specific enolase (NSE: neuronal glycolytic enzyme) and S-100B (glial cell protein) during and after CEA. METHODS: 27 patients with symptomatic carotid artery disease (70-99% stenosis) underwent CEA, 14 under LA and 13 under GA. Jugular venous blood samples were assayed for NSE and S-100B before carotid clamping and at 5min before and 5min, 2, 4, 6, 8, 12 and 24h after clamp release. RESULTS: No neurological complications occurred. S-100B levels were low and did not increase from baseline in either group. Pre-clamp NSE levels were similar in both groups (LA: 17.6 (15.2-20.7)microg/l, GA: 21.5 (11.3-26.2)microg/l; p=0.37) but increased significantly 2h after clamp release in GA patients (LA: 25.5 (16.6-27.8)microg/l, GA: 48.2 (31.4-61.3)microg/l, p=0.05) with a significant rise from baseline in GA patients (p=0.04). CONCLUSIONS: CEA performed under GA is associated with greater rises in jugular venous NSE, and hence cerebral injury, than CEA performed under LA.

Plasma homocysteine concentrations and the single nucleotide polymorphisms in the methionine synthase gene (MTR 2756A>G): Associations with the polycystic ovary syndrome An observational study.

BACKGROUND: Elevated plasma homocysteine (Hcy) is a recognized risk factor for cardiovascular disease (CVD) and other defects. Biochemical and genetic studies have characterized molecular determinants contributing to alter Hcy metabolism. The vitamin B12 dependent enzyme methionine synthase (MTR) regulates de novo production of methionine from homocysteine. Defects in the activity of this enzyme may possibly predispose to higher plasma Hcy concentrations. STUDY DESIGN: We examined the associations between plasma Hcy concentrations and a single nucleotide polymorphism (SNP) in the MTR gene (MTR 2756A>G), and plasma folate concentrations, in 71 women (Caucasian and South Asian) attending a fertility clinic. We also determined the ethnic variations in the frequencies of the 3 genotypes of the MTR 2756 A>G gene. RESULTS: The frequency of the variant G allele was similar in the Caucasians and the South Asians (OR: 1.83; 95% CI: 0.79-4.23, p=0.2). The frequency was also similar in the PCOS and non-PCOS groups (OR: 0.88; 95% CI: 0.39-1.99). Plasma Hcy levels were significantly higher in women with PCOS compared with non-PCOS controls (p=0.05) and in Caucasian women with PCOS compared with Caucasian controls (p=0.04) in the presence of the MTR 2756 AA genotype (wild type). After adjusting for age, BMI, waist circumference and ethnicity, the significant predictors of plasma Hcy concentrations were plasma LDL, whole blood folate concentrations and a clinical diagnosis of PCOS. CONCLUSIONS: The important predictors of plasma Hcy concentration in women of reproductive age are whole blood folate concentrations, a background of PCOS and plasma LDL concentrations. The SNP 2756 A>G in the MTR gene does not appear to influence the plasma Hcy levels.

Utility of biochemical screening in the context of evaluating patients with a presumptive diagnosis of osteoporosis.

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.

High-dose oral colecalciferol loading in obesity: impact of body mass index and its utility prior to bariatric surgery to treat vitamin D deficiency.

Obesity is associated with lower vitamin D levels compared with normal weight subjects, and if levels are not replaced prior to bariatric surgery, this can increase fracture risk as bone density typically falls post-operatively. We analysed the effect of body mass index (BMI) on vitamin D levels in response to 300 000 IU of colecalciferol in patients with vitamin D deficiency (<30 nmol L-1 ). Patients were grouped according to their BMI as normal weight (20-24.9 kg m-2 ), overweight (25-29.9 kg m-2 ), obese class I (30-34.9 kg m-2 ) and obese class II and above (>35 kg m-2 ). The records were retrospectively analysed to investigate the effects of BMI on vitamin D (total 25-hydroxy vitamin D [25(OH)D]), serum Ca2+ and parathyroid hormone (PTH) levels at 6, 12, 26 and 52 weeks compared with baseline. Compared with normal weight subjects, overweight and obese patients achieved lower mean peak total 25(OH)D levels (6 weeks post-loading), which was most significant in the class II and above group (mean total 25(OH)D levels 96.5 ± 24.2 nmol L-1 and 72.42 ± 24.9 nmol L-1 , respectively; P = 0.003). By 26 weeks, total 25(OH)D levels fell in all groups; however, there was now a significant difference between the normal weight subjects and all other groups (mean total 25(OH)D levels 84.1 ± 23.7 nmol L-1 ; 58 ± 20 nmol L-1 , P = 0.0002; 62.65 ± 19.2 nmol L-1 , P = 0.005; 59.2 ± 21 nmol L-1 , P = 0.005, respectively). Far fewer patients in the overweight and obese groups maintained levels above the recommended level of 75 nmol L-1 52 weeks post-loading (93%; 20%, P = 0.0003; 23%, P = 0.01; and 14%, P = 0.001, respectively). Alternative regimes for the treatment of vitamin D deficiency are needed in overweight and obese patients, especially those in whom bariatric surgery is planned.

Empowering primary care to tackle the obesity epidemic: the Counterweight Programme.

OBJECTIVE: To improve the management of obese adults (18-75 y) in primary care. DESIGN: Cohort study. SETTINGS: UK primary care. SUBJECTS: Obese patients (body mass index > or =30 kg/m(2)) or BMI> or =28 kg/m(2) with obesity-related comorbidities in 80 general practices. INTERVENTION: The model consists of four phases: (1) audit and project development, (2) practice training and support, (3) nurse-led patient intervention, and (4) evaluation. The intervention programme used evidence-based pathways, which included strategies to empower clinicians and patients. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation. MAIN OUTCOME MEASURES: Proportion of practices trained and recruiting patients, and weight change at 12 months. RESULTS: By March 2004, 58 of the 62 (93.5%) intervention practices had been trained, 47 (75.8%) practices were active in implementing the model and 1549 patients had been recruited. At 12 months, 33% of patients achieved a clinically meaningful weight loss of 5% or more. A total of 49% of patients were classed as 'completers' in that they attended the requisite number of appointments in 3, 6 and 12 months. 'Completers' achieved more successful weight loss with 40% achieving a weight loss of 5% or more at 12 months. CONCLUSION: The Counterweight programme provides a promising model to improve the management of obesity in primary care.

How Useful are Laboratory Practice Guidelines?

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 are involved, CPGs can provide practical information which supports local laboratories as well as clinicians in the implementation and appropriate use of recommendations. Implementation of CPGs is an often neglected area that needs attention and thought. There are many barriers to successful implementation, which may vary at local level. These need to be identified early if CPGs are to be successfully adhered to. The effectiveness of CPGs also needs to be audited using process and health outcome indicators. Clinical audit is an effective tool for assessing adherence to recommendations and for measuring the impact and success of the CPG.

Lipogenesis by isolated human apocrine sweat glands: testosterone has no effect during long-term organ maintenance.

Lipid synthesis by freshly isolated human apocrine glands has been measured by the incorporation of [U-14C] acetate. Incorporation is linear over 6 h at 1010 +/- 282 pmol/mg wet weight/h (n = 11; mean +/- sem). The lipid classes, as percentages of the total lipid synthesized, were found by TLC to be cholesterol 12.3 +/- 2.0, mono-glycerides 7.5 +/- 1.5, 1,2 di-glycerides 3.0 +/- 0.9, 1,3 di-glycerides 3.5 +/- 0.5, tri-glycerides 28.4 +/- 1.8, free fatty acids 2.0 +/- 0.4, lysolecithin 15.4 +/- 3.9, sphingomyelin 9.9 +/- 4.3, phosphatidyl-choline 8.4 +/- 0.4, phosphatidyl-ethanolamine -inositol and -serine 1.8 +/- 0.1, phosphatidic acid and cardiolipin 3.3 +/- 0.5, and unidentified 3.3 +/- 0.5 (mean +/- sem, n = 5). Glands were maintained on permeable supports. After 10 d maintenance, electron microscopy showed that the cellular architecture had been preserved, that the ATP contents were the same as in freshly isolated glands, and that [U-14C] acetate incorporation was not significantly altered at 851 +/- 237 pmol/mg/h (n = 18). The addition of 3 microM testosterone had no effect on acetate incorporation at 844 +/- 231 pmol/mg/h (n = 18). The lipid classes and their proportions were similar to the values for fresh glands after 10 d maintenance both with and without testosterone.

Spironolactone is an effective and well tolerated systemic antiandrogen therapy for Hirsute women.

We treated 22 hirsute women with spironolactone in an open trial to determine whether it caused objective changes in hair growth. Among them, 18 women completed 12 months therapy with 200 mg spironolactone daily. During this period, the mean daily linear growth rates of hair on the face, abdomen, and thigh were reduced to 66% (P less than 0.001), 75% (P less than 0.01), and 72% (P less than 0.001) of their pretreatment values. The mean hair shaft diameters were reduced to 83% (P less than 0.01) on the face, 88% (P less than 0.001) on the arm, 74% (P less than 0.01) on the abdomen, and 80% (P less than 0.001) on the thigh. Daily hair volume production was calculated from the diameter and daily growth rate; it was reduced to 60% (P less than 0.01) on the face, 52% (P less than 0.01) on the arm, 34% (P less than 0.001) on the abdomen, and 48% (P less than 0.001) on the thigh. Six of the 18 women who completed the study developed midcycle vaginal bleeding, and 3 women had previously irregular menstrual cycles regulated. We conclude that spironolactone is effective and well tolerated for hirsute women.