Hypoglycaemic episodes in patients with type 2 diabetes--risk factors and associations with patient-reported outcomes: The PANORAMA Study.

AIM: To explore the frequency of hypoglycaemic episodes, their risk factors, and associations with patient-reported outcomes in patients with type 2 diabetes enrolled in the PANORAMA cross-sectional study. METHODS: Five thousand seven hundred and eighty-three patients aged ≥ 40 years with type 2 diabetes duration ≥ 1 year were recruited in nine European countries. Patients reported severe and non-severe hypoglycaemic episodes during the past year at a single study visit. Patient-reported outcomes were measured by the Audit of Diabetes-Dependent Quality of Life, Diabetes Treatment Satisfaction Questionnaires, Hypoglycaemia Fear Survey-II, and EQ-5D Visual Analog Scale. RESULTS: During the previous year, 4.4% of the patients experienced ≥ 1 severe hypoglycaemic episode; among those without severe hypoglycaemia, 15.7% experienced ≥ 1 non-severe episode. Patients experiencing any hypoglycaemic episode reported a greater negative impact of diabetes on quality of life, greater fear of hypoglycaemia, less treatment satisfaction and worse health status than those with no episodes. In multivariate analyses hypoglycaemia was significantly associated with longer diabetes duration; presence of microvascular and, to a lesser extent, macrovascular complications; treatment with insulin, glinides or sulfonylureas; and use of self-monitoring blood glucose. CONCLUSION: In patients with type 2 diabetes, severe hypoglycaemic episodes were not uncommon and one in five experienced some form of hypoglycaemia during the previous year. Hypoglycaemia was associated with more negative patient-reported outcomes. The risk of hypoglycaemia increased with diabetes duration, presence of diabetes-related complications, use of self-monitoring blood glucose, insulin secretagogues, and insulin treatment.

COPD awareness survey: do Belgian pulmonary physicians comply with the GOLD guidelines 2010?

Chronic Obstructive Pulmonary Disease (COPD) is underestimated, underdiagnosed and often under-treated in the general population. A survey of 17 structured questions, delivered to all Belgian pulmonary physicians (PPs) (116 responses), evaluated diagnosis and treatment strategies in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2010 and assessed opinions about the importance of diurnal variation of COPD symptoms. All COPD diagnoses (37% new cases) were spirometry confirmed. Main diagnostic parameters were symptoms (99%), external risk factors (99%), clinical examination (97%), exacerbations (96%) and patient mobility (96%). FEV1 (forced expiratory volume in 1s) (97%) or FEV1/FVC (ratio of FEV1 to forced vital capacity) (93%) were used most to assess diagnosis and severity. The 3 most important therapeutic objectives were symptom relief, preventing exacerbations, and improving quality of life; if these were not reached, the preferred strategy (60% of PPs) was adding another medication. Treatment strategies varied with COPD stage: short-acting beta2-agonists (90%) and short-acting anti-cholinergics (59%) were used for GOLD I disease, whereas for higher stages long-acting beta2-agonists (36-48%) and long-acting anti-cholinergics (79%) were given with inhaled corticosteroids (21-67%). Symptoms were perceived to vary throughout the day, affecting quality of life (97%) and mobility (89%). In particular, respiratory symptoms were more severe in the morning (51-92%), leading PPs to adapt treatment (69%). This survey demonstrated that management of COPD by PPs in Belgium is generally in line with the GOLD guidelines 2010 and that they perceive morning symptoms as being frequent and having an impact on patient's life.

[Evaluation and care of patients with type Ii diabetes regarding recommendations concerning cardiovascular risk factors and adherence to values in general medicine in the Grand Duchy of Luxembourg]. / Evaluation de la prise en charge des patients diabétiques type II vis-à-vis des recommandations concernant les facteurs de risque cardiovasculaires et l'atteinte des valeurs cibles en médecine générale au Grand Duché de Luxembourg.

AIMS: The objective of this study was to assess the adherence to national guidelines on cardiovascular prevention and target attainment for patients with type 2 diabetes mellitus followed-up in general practice. METHODS: Non-interventional, cross-sectional survey. RESULTS: 606 patients have been considered in this analysis. Type 2 diabetes patients remain undertreated with statins (63% treated), even so those with a cardiovascular history (80% treated). Although more patients received antihypertensive treatment (82%) compared to hypolipidemic medication (69%), the proportion of patients attaining targets for total (35%), HDL (65%), and LDL-cholesterol (42%) exceeded far those attaining blood pressure control (13%). The primary endpoint of reaching the goal for LDL-cholesterol (<100 mg/dL) was attained by 42% of patients, of which only 13% reached the more stringent target of LDL-C <70 mg/dL. About half of the patients attained glycemic control (HbA1c <7%, 49%) and had triglycerides <150 mg/dL (55%). CONCLUSIONS: The majority of type 2 diabetes patients are treated for hypercholesterolemia and hypertension, although, there is still undertreatment with statins, especially in patients with CV disease. Only 42% of patients were on target for LDL-cholesterol and 13% for blood pressure. Therefore, wider implementation of process and outcome indicators, which proved to be related, and continuous evaluation of their result, is needed.

Organization of a quality-assurance project in all Belgian multidisciplinary diabetes centres treating insulin-treated diabetes patients: 5 years' experience.

AIMS: To describe the IQED, a quality-assurance system started in 2001 in Belgian hospital-based multidisciplinary diabetes centres, and its effects on the quality of care. METHODS: The study was conducted through four data collections (in 2001, 2002, 2004 and 2006). Approximately 120 diabetes centres provided data on a systematic random sample of 10% of their adult diabetic patients on at least two daily insulin injections. Data on patient characteristics, glycaemic control, cardiovascular risk, diabetes complications, follow-up procedures and treatment were obtained. Local quality promotion was encouraged by returning comprehensive feedback (benchmarks) and during information meetings. RESULTS: Nearly all diabetes centres (98-100%) participated. The pooled sample consisted of 9194 (32%) Type 1 and 19 828 (68%) Type 2 diabetes patients, with mean diabetes duration of 17 years and 14 years, prevalence of microvascular complications of 23% and 38% and prevalence of macrovascular complications of 9% and 26%, respectively. At the start, the quality of care was good in terms of risk-factor testing rates and moderate in terms of patients meeting goals for risk-factor management. At least 50% of the centres initiated quality-promoting initiatives. After 5 years, significant improvements were seen in risk-factor testing rates, apart from renal screening. Improvements in intermediate outcomes were less obvious, apart from an increase in patients reaching the targets for blood pressure and LDL cholesterol. CONCLUSIONS: It is feasible to implement a continuous quality-improvement project on a nationwide scale, with improvements particularly in process indicators.

Functional testosterone: biochemical assessment of hypogonadism in men--report from a multidisciplinary workshop hosted by the Ontario Society of Clinical Chemists.

OBJECTIVES: In 2004, the Ontario Society of Clinical Chemists (OSCC) held an invitational multidisciplinary workshop to establish the most reliable, cost-effective approach to the biochemical assessment of hypogonadism in men. METHODS: Specialists across Canada in clinical biochemistry, endocrinology, family medicine and urology were invited to participate in this workshop which included individual presentations and a consensus component addressing two challenge statements: 1) 'Determinations for total testosterone (TT) are equivalent to those for bioavailable testosterone (BAT) or calculated BAT (cBAT) or free testosterone (FT) (by analogue radioimmunoassay or equilibrium dialysis) or calculated FT (cFT)'; 2) 'There is no good evidence that borderline low testosterone concentrations in men should be treated'. The main outcomes were to identify what agreement exists in Canada, what issues were still controversial, and what research remains to be addressed. RESULTS: Six recommendations based on expert opinion addressed these main themes: investigate with morning total testosterone (TT) followed by repetition and reflexive testing of sex hormone binding globulin (SHBG) if testosterone is 8-15 nmol/L with automatic calculation of cBAT; discontinue the use of analogue free testosterone assays; and definitive methods and standards must be available to ensure standardized results. CONCLUSIONS: Total testosterone is a reliable marker for the initial investigation of men presenting with symptoms of hypogonadism; cBAT is a reasonable follow-up test in patients with equivocal biochemical or consistent symptomatic findings.

Collecting information on the quality of prescribing in primary care using semi-automatic data extraction from GPs' electronic medical records.

OBJECTIVES: To evaluate a semi-automatic data extraction from the electronic medical record (EMR) of general practitioners (GPs) through a comparison with a paper sheets data collection simultaneously used in a primary care research project on the quality of prescribing for osteoarthritis in the elderly. SUBJECTS: One hundred and fifty-two GPs using five different EMR-software systems participated with the semi-automatic data extraction from the EMR and 233 GPs collected data with paper registration sheets. METHODS: The proportion of patients with respectively a drug prescription, paracetamol, a non-steroidal anti-inflammatory drug (NSAID) and ibuprofen were compared between the semi-automatic extraction and the paper data collection and among the EMR-software systems. RESULTS: Using the semi-automatic data extraction, a significantly lower proportion of patients on drugs was obtained compared to the paper data collection (adjusted OR: 0.31; 95% CI 0.25-0.39). However, the proportion of patients on a specific type of drug was comparable. Within the results from the semi-automatic extraction, the results were heterogeneous among the different EMR-software systems. CONCLUSIONS: The semi-automatic data extraction with multiple EMR-software systems proposed in this study seems suitable for quality of prescribing assessment in primary care. However, it may be less reliable when only a single EMR-software is used.

Detection of HCV antibodies in oral fluid.

Although conventionally the detection of HCV antibodies is carried out on serum, the collection of oral fluid is non-invasive, safe and cost effective. In this study, the efficacy of the detection of HCV antibodies in oral fluid was assessed. 73 anti-HCV positive and 73 anti-HCV negative paired serum/oral fluid samples, drawn from patients visiting a Belgian academic hospital, were tested using the modified Ortho HCV 3.0 and LIA confirmation assay. Performing the test on oral fluid with the modified protocol, 61/73 anti-HCV positive samples were tested positive, while 73/73 anti-HCV negative samples were tested negative, giving a sensitivity and specificity of 83.6% (95% CI: 72.7-90.9%) and 100.0% (95% CI: 93.8-100.0%), respectively. Comparing S/CO of concordantly positive and negative samples, the cut-off point was lowered by 30% resulting in a sensitivity of 89.0% (95% CI: 79.0-94.8%) while the specificity remained 100.0% (95% CI: 93.8-100.0%). The confirmation assay was carried out as described by the manufacturer, diluting the oral fluid 1:10. Testing paired samples gave a concordance of 85.6% (125/146), yielding no more accurate results. These findings suggested that the modified ELISA method for anti-HCV detection in oral fluid can be used for epidemiological surveys.

Higher attack rates for left motor deficit among men with cerebrovascular events.

The authors report the findings of a prospectively collected database of stroke and TIA recorded from 1998 through 1999 by the 178 family physicians of the Belgian sentinel network. The yearly age-adjusted attack rate per 100,000 men was estimated as 109 (95% CI = 86 to 137) for left motor deficit and 75 (95% CI = 56 to 99) for right motor deficit (p = 0.011). This difference was not observed among women nor in the entire sample population. The authors suggest that handedness should be systematically recorded and compared to both sex and the side of the event.

Assessment of a three-year experience with a Belgian Primary Care data Network.

The paper describes the experiences with a Belgian Primary Care data Network from 1999 till 2002. Three cycles of data collection have been performed. The network involves about 300 general practitioners (GPs) and up to 8 different software packages. This network is semi-anonymous, semi-automatic and mixed (paper and electronic with various software's). For the coming next years, efforts should be focused on solving some frequently occurring problems with the data collection through the EPR, such as a considerable number of data lacking and the fact that GPs do not always use the problem oriented structure of the EPR (Electronic Patient Record). Afterwards, more promising usage could be considered and developed such as repeated data collection using a same GPs' sample, long-term recording studies, usage of larger GPs' samples, etc.

Precision and method bias of two assays for oestradiol: consequences for decisions in assisted reproduction.

Oestradiol monitoring in assisted reproduction is empirical, with no proof of benefit. Precise oestradiol estimation will be an essential pre-requisite for high quality evaluation of possible differences between combined and ultrasound-only monitoring. Objectives of the present trial were independent method comparison and bias estimation of chemiluminescent immunoassay (CLIA) versus radioimmunoassay for oestradiol. In a prospective comparison, 505 consecutive samples were split and assayed concurrently. Precision (reproducibility), relative bias and logistics were analysed and compared to manufacturers' findings. Correlation between CLIA and radioimmunoassay was excellent. Positive bias with CLIA necessitated altering decision points for therapy. Precision (reproducibility) was superior with CLIA, making it an appropriate candidate method for future randomized trials of the effectiveness of combined oestradiol/ultrasound monitoring for assisted reproduction.

Does thiopentone delay recovery in children premedicated with midazolam?

This prospective, randomized trial of paediatric surgical outpatients, premedicated with oral midazolam, was designed to determine if an intravenous thiopentone induction of anaesthesia prolongs postoperative recovery compared to an inhalation induction with halothane. One hundred children, one to ten years of age, undergoing ENT surgical procedures of 30-60 min duration received midazolam 0.5 mg.kg-1 with atropine 0.03 mg.kg-1 and were randomized to either halothane (Group 1, n = 50) or a thiopentone induction (Group 2, n = 50) technique, followed by a standardized anaesthetic-protocol. Time to extubation was significantly greater in the thiopentone group (8.8 +/- 4 min vs 7.1 +/- 3 min, P < 0.05). Patients receiving thiopentone were also more sedated than the halothane group on arrival in the PARR (3.9 +/- 1.5, 3.3 +/- 1.7, respectively P < 0.05), but the differences disappeared after 30 min. Children premedicated with oral midazolam who receive an intravenous thiopentone induction have a slightly prolonged emergence from anesthesia compared to children induced with halothane.

Amikacin pharmacokinetics and suggested dosage modifications for the preterm infant.

The pharmacokinetics of amikacin administered intravenously at currently recommended doses (7.5 mg/kg every 12 h for infants with less than 7 days of life; 7.5 mg/kg every 8 h for infants with greater than 7 days of life) were studied in 28 preterm infants weighing less than 2,500 g (mean +/- standard deviation, 1.38 +/- 0.47 kg; postconceptional age, 30.50 +/- 2.86 weeks). The medication was infused over 45 min. Trough and peak serum samples as well as two additional samples were taken at steady state. The results showed a statistically significant inverse relationship between half-life (8.42 +/- 2.55 h) and postconceptional age (P = 0.002) and a direct correlation between total body clearance (0.84 +/- 0.28 ml/min per kg) and postconceptional age (P = 0.02). These pharmacokinetic data were used to calculate a new dosage schedule for preterm infants. The derived intravenous dosage of amikacin for infants of less than 30 weeks of postconceptional age was 9 mg/kg every 18 h. For infants of greater than 30 weeks of postconceptional age, the dosage was 9 mg/kg every 12 h. Peak and trough levels of amikacin in serum that fell within the therapeutic range were compared by using the currently recommended dosage schedule and the dosage schedule derived from our pharmacokinetic data. There was a reduction in the number of peak and trough levels that fell outside the accepted therapeutic range which was not statistically significant. Extension of the dosing interval and a further increase in the dosage may result in further improvement. Based on these data, the current recommendations are inadequate for the preterm infant. Our derived dosage schedule improved but did not eliminate high trough and low peak levels of amikacin in all infants. The current recommendations should be adjusted for the preterm infant. Ongoing therapeutic drug monitoring is essential to tailor the amikacin dosage to the individual patient.

Assessment of immediate post-anaesthetic recovery in young children following intravenous morphine infusions, halothane, and isoflurane.

Within 15 minutes of terminating general anaesthesia, progressive recovery of consciousness, spontaneous ventilation and cough, and limb movements were assessed in 60 young children (age range 0-5 years, mean +/- SEM; 2.83 +/- 0.34; weight 13.86 +/- 0.41 kg). All patients were ASA physical status class I-III, received a standard intravenous induction (atropine 0.02 mg X kg-1, thiopental sodium 5 mg X kg-1, diazepam 0.2 mg X kg-1), were intubated with an orotracheal tube following the administration of metocurine, 0.4 mg X kg-1, and were maintained under general anaesthesia with nitrous oxide and oxygen in a 70:30 mixture administered by a T-piece circuit. They were ventilated mechanically to maintain normal blood-oxygen tension and normocarbia. The patients were assessed in three equal groups according to the anaesthetic supplement they received. Group I received intravenous infusions of morphine sulfate (loading dose 60 micrograms X kg-1 administered over 5 minutes followed by a continuous intravenous infusion of 2 micrograms X kg-1 X min-1. Patients in Groups II and III had 0.5 per cent halothane and 1.0 per cent isoflurane respectively added to the nitrous oxide/oxygen fresh gas mixture rather than morphine sulphate infusions. By the end of the study period, there was no significant difference in the degree of recovery between the morphine and the isoflurane groups but the patients in the halothane group had recovered to a lesser degree. Generally, the patients in the morphine group were awake but not crying, while those in the other two groups were less sedated.

Pharmacokinetics of intravenous morphine in balanced anesthesia: studies in children.

Intravenous morphine in combination with muscle relaxants, nitrous oxide, and oxygen in so-called balanced anesthesia is commonly used in children between the ages of 0 and 5 yr during surgery. We define dosing rules for a loading dose followed by a continuous intravenous infusion of morphine sulfate to achieve a serum morphine concentration of 75 micrograms/L. This concentration is well above the minimum serum morphine concentration of 50 micrograms/L for moderate analgesic effects in adults. It also exceeds the concentration of 65 micrograms/L claimed to provide adequate analgesia in children during surgery. The clearance of morphine in 8 children between 0 and 5 yr of age was 20.5 +/- 2.8 mL/kg/min (means +/- SD). This result is threefold larger than the clearance value obtained after a single intravenous dose and 1.5 times greater than clearance values found after multiple intravenous doses of morphine, previously reported by others in children between the ages of 1 and 15 yr. Having established a dosing regimen that achieves a steady-state serum morphine concentration of approximately 75 micrograms/L, we plan to investigate the relationship between morphine serum concentration and pharmacologic effect. Intraoperatively the action of morphine at its receptor site will be assessed according to a scoring system including EEG changes, heart rate, blood pressure, response to sensory stimuli, and maintenance of vital functions. The effect of intravenous morphine will further be estimated according to the postanesthetic scoring system described in this report. Using intraoperative and postanesthetic scores to evaluate the pharmacodynamics of morphine for anesthesia in relation to morphine serum concentration will lead to a better understanding and improvement in use of intravenous morphine in young children.

Analysis of morphine in serum by high performance liquid chromatography with amperometric detection.

In this report we describe a rapid and sensitive micromethod using high performance liquid chromatography (HPLC) with electrochemical detection (ED) to measure morphine concentration in serum or plasma. The separation of morphine and the internal standard 5-hydroxyquinoline, from interfering compounds present in plasma was achieved by paired-ion reverse phase chromatography using a 70 mM phosphate buffer at pH 5.80. The flow rate was 1 ml/min. Oxidation of morphine and the internal standard was obtained at a potential of 0.60 V. Only 100 microliter of serum or plasma was required. Analytical recoveries for morphine and 5-hydroxyquinoline were determined as 78% and 63% respectively. The between-day precision of serum samples containing 250, 100, and 25 microgram/L of morphine (n = 20) was 6.5%, 5.2%, and 9.5% respectively. The detection limit was determined as 1 microgram/L at a sensitivity of 5 nA/V. In our preliminary studies, 3 children between the ages of 0 and 5 years received a bolus of morphine of 11 microgram/kg, followed by an infusion of 2 microgram/kg/min during surgery. The time-concentration curves demonstrate an initial rapid fall in morphine concentration with subsequent attainment of a steady state concentration of approximately 90 microgram/L after 1 h. This concentration would be expected to produce optimal analgesia in conscious patients.

Ranitidine kinetics and dynamics. I. Oral dose studies.

Ranitidine, an H2-receptor antagonist, has been shown to reduce pentagastrin-stimulated gastric secretion. We examined the relationship between inhibition of gastric secretion and ranitidine serum concentration. Twelve normal male subjects received 20, 40, or 80 mg of ranitidine orally 90 min before starting a 3-hr continuous infusion of pentagastrin, 2 micrograms/kg/hr. Ranitidine, 20, 40, and 80 mg, reduced hydrogen ion output by 29%, 50%, and 70% and secretion volume by 21%, 37%, and 47%. Pepsin activity was reduced by 8%, 50%, and 49% by the same doses. Peak serum concentration was correlated positively with percent reduction in hydrogen ion output (r = 0.81, P less than 0.001) and volume (r = 0.71, P less than 0.01) over a 2-hr period. A 50% inhibition of hydrogen ion output was associated with a peak ranitidine serum concentration of 165 micrograms/l and subjects reached peak serum concentration 60 to 120 min after oral dosing. An appropriate therapeutic effect should be achieved with 8 hourly doses of 80 mg ranitidine. No clinically significant subjective or toxic biochemical effect of ranitidine was seen after single doses. White blood cell count was reduced in 11 of 12 subjects 7 days after ranitidine, an observation which calls for further investigation.

Ranitidine kinetics and dynamics. II. Intravenous dose studies and comparison with cimetidine.

Intravenous ranitidine has been shown to reduce pentagastrin-stimulated gastric secretion. Eight normal men received, in randomized order, 60 mg ranitidine or 300 mg cimetidine intravenously over 2 min. Both ranitidine and cimetidine induced decreases in volume hydrogen ion content and pepsin activity of stimulated gastric juice. Ranitidine half-life (t1/2) was 2.1 +/- 0.1 hr and cimetidine (t1/2) was 1.5 +/- 0.1 hr. Ranitidine volume of distribution was 1.6 +/- 0.1 l/kg and that of cimetidine was 1.12 +/- 0.12 l/kg. The clearance of ranitidine was 0.54 +/- 0.04 l/kg hr-1 and that of cimetidine was 0.5 +/- 0.05 l/kg hr-1. It is suggested that the intravenous loading dose of ranitidine necessary to attain a serum concentration of 200 micrograms/l (which would achieve a 50% inhibition of gastric acid) is 0.3 mg/kg, followed by an infusion rate of 0.11 mg/kg hr-1.

Analysis of ranitidine in serum by high performance liquid chromatography.

We describe a simple and rapid micro method for the high pressure liquid chromatographic analysis of ranitidine, N-[2[[[5-[(dimethylamino)-methyl]-2-furanyl]methyl]thio]-ethyl-N'-methyl-2-nitro-1,1-ethenediamine in serum or plasma. The percentage analytical recovery of ranitidine and internal standard (metiamide) was 99% and 81%, respectively. The between-day precision of the procedure (n = 20) at ranitidine plasma concentrations of 500, 250, and 125 microgram/liter generated coefficients of variation of 6.2, 8.7, and 8.9%, respectively. The method was applied in preliminary studies to correlate serum concentrations of ranitidine with gastric acid secretion after continuous pentagastrin stimulation (2 microgram/kg/hr) in patients receiving an oral dose of 20, 40, or 80 mg of the drug.