Pilot study to assess measures to be used in the prospective audit of the management of foot ulcers in people with diabetes.

AIM: To design and test a methodology for assessing aspects of the management of foot disease in diabetes. METHODS: A national working group devised pilot datasets that may be used to document the process of management of active ulceration. Participating volunteer specialist units throughout England were required to characterize newly presenting people with diabetic foot ulcers using a standard questionnaire comprising the dataset and to document outcomes at 6 and 12 months. Semi-structured interviews were later conducted with the volunteers at the units. RESULTS: A total of 23 units recorded baseline data on 652 people with incident foot ulcers; valid outcome data were available for 541 people (83.0%). Of the 541 index ulcers, 351 (64.9%) healed within 24 weeks, with a median time to healing of 63 days. Ulcer site and depth and peripheral arterial disease were associated with differing ulcer healing rates. By contrast, baseline demographic characteristics were not independently associated with healing. These were used to calculate a standardized case-mix adjusted healing ratio. In most units data collection took < 10 min per person, but participants reported that the burden of local data collection was still excessive. CONCLUSION: This study confirmed the feasibility of routine multi-unit comparative assessment of care of the foot in diabetes, including the generation of meaningful service reports, but for general use the burden of local data collection will need to be reduced (e.g. by using linkage to existing national data collections).

Women with pre-gestational diabetes have a higher risk of stillbirth at all gestations after 32 weeks.

AIM: To explore the additional risk of stillbirths and to quantify that risk according to gestational age among women with diabetes. METHODS: Data on pregnancies ending in 2007 and 2008 in women with pre-gestational diabetes in three English regional audits were identified. A prospective audit collected data on all pregnancies delivering between June 2010 and May 2011 in one region and in 13 other units across England. The data on all singleton pregnancies from these two cohorts were combined. Comparisons were made to all births in England and Wales for the same time period using data from the Office for National Statistics. RESULTS: In the cohort of women with pre-gestational diabetes there were a total of 2085 singleton pregnancies, of which 29 resulted in a stillbirth (overall stillbirth rate 13.9 per 1000, 95% CI 9.7-19.9, relative risk compared with all pregnancies in England and Wales 2.73, 95% CI 2.61-2.84). The relative risk of stillbirth between 32 and 34 weeks' gestation was 4.95 (95% CI 4.24-5.78), 3.77 (95% CI 3.42-4.16) at 35 to 36 weeks, 5.75 (95% CI 5.43-6.09) for deliveries at 37 or 38 weeks and 7.34 (95% CI 6.52-8.25) for those born at 39 weeks or more. CONCLUSION: Women with diabetes have a significantly higher risk of stillbirth at all gestations after 32 weeks and this additional risk is not just confined to pregnancies at 37 weeks or more.

Excess mortality during hospital stays among patients with recorded diabetes compared with those without diabetes.

AIM: To assess the additional mortality during hospital admissions among patients with recorded diabetes and identify the extent of variation in English provider trusts. METHODS: Inpatient admissions to all English hospitals between April 2010 and March 2012 were extracted from Hospital Episode Statistics. Binary logistic regression was used to standardize for age, sex, deprivation, method and reason for admission, co-morbidities and type of trust. Trust level standardized mortality ratios for inpatients with recorded diabetes were compared with those without recorded diabetes and with published measures of hospital mortality. RESULTS: Of the 10 169 003 hospital admissions analysed, 11.2% had recorded diabetes, but 21.5% of inpatient deaths occurred in this group. After adjustment for case mix, hospital admissions in patients with recorded diabetes had a 6.4% greater risk of dying (2052 more deaths over 2 years) than would be expected compared with similar patients without recorded diabetes. The additional risk of death was significantly greater in smaller trusts. The highest additional risk of death was found in hospital admissions of younger female patients admitted electively. At provider trust level, 37.4% of variation in adjusted mortality in patients with recorded diabetes was explained by the mortality in those without recorded diabetes. CONCLUSION: A diagnosis of diabetes has an adverse impact on hospital mortality that cannot be explained by usual case-mix adjustments, and the additional risk of dying is greatest among hospital admissions that would normally have a low risk of death. This implies that diabetes may override the usual risk factors for hospital mortality.

Variation in the recorded incidence of amputation of the lower limb in England.

AIMS/HYPOTHESIS: The study aimed to explore the variation in recorded incidence of lower limb amputation in England. METHODS: The incidences of amputations in adults with and without diabetes were determined from hospital episode statistics over 3 years to 31 March 2010 and compared between the 151 Primary Care Trusts (PCTs) in England. RESULTS: There were 34,109 amputations, including 16,693 (48.9%) in people with diabetes. The incidence was 2.51 per 1,000 person-years in people with diabetes and 0.11 per 1,000 person-years in people without (relative diabetes risk 23.3). Incidence varied eightfold across PCTs in people both with diabetes (range 0.64-5.25 per 1,000 person-years) and without (0.03-0.24 per 1,000 person-years). Amputations in people with diabetes varied tenfold--both major (range 0.22-2.20 per 1,000 person-years) and minor (range 0.30-3.25 per 1,000 person-years). The incidences of minor and major amputations were positively correlated both in those with (r = 0.537, p < 0.0005) and without (r = 0.611, p < 0.0005) diabetes. Incidences of amputations were also correlated between people with and without diabetes (total amputations r = 0.433, p < 0.0005; major amputations r = 0.528, p < 0.0005). There was a negative correlation between the incidence of amputation and estimated prevalence of ethnic Asians. No association was found between the PCT incidence of either total amputations and general population prevalence of social deprivation (r = -0.138, p = 0.092) or smoking (r = 0.137, p = 0.096). CONCLUSIONS/INTERPRETATION: Variation in amputation incidence occurs across England. Because of the similarity in amputation variation between people with and without diabetes the variation may reflect generic differences in local healthcare delivery, although racial factors may also contribute.

The Association of Public Health Observatories (APHO) Diabetes Prevalence Model: estimates of total diabetes prevalence for England, 2010-2030.

AIM: To provide robust estimates of the total prevalence of diabetes (including undiagnosed) in England to support effective planning and delivery of services. METHODS: Age- and sex-specific prevalence of diagnosed and undiagnosed diabetes in people aged 16 years and older [based on HbA(1c) of 6.5% (48 mmol/mol) or greater] were taken from the Health Survey for England 2006. Data from the Health Survey for England 2004 were used to adjust for ethnic difference in prevalence. A deprivation adjustment refined the geographical distribution of diabetes prevalence. Projected diabetes prevalence was calculated using trends in overweight and obesity prevalence from the Health Surveys for England 2003 to 2008. RESULTS: In 2010 there were an estimated 3.1 million (7.4%) people aged 16 years and older with diabetes in England. Comparisons between the 2008/2009 Quality and Outcomes Framework data and estimates for 2009 suggest that that 27.1% of the total number of people with diabetes are not included on general practice diabetes registers. The total number of adults with diabetes is projected to rise to 4.6 million or 9.5% by 2030. Approximately half of this increase is attributable to the changing age and ethnic group structure of the population and half is because of the rising prevalence of obesity. CONCLUSIONS: This model estimates that the prevalence of total diabetes (diagnosed and undiagnosed) in England is higher than previously suggested. An ageing population and increasing prevalence of obesity imply that the prevalence of diabetes will continue to rise and health services should be planned accordingly.

Development and evaluation of a standardized registry for diabetes in pregnancy using data from the Northern, North West and East Anglia regional audits.

OBJECTIVES: To develop and evaluate a standardized data set for measuring pregnancy outcomes in women with Type 1 and Type 2 diabetes and to compare recent outcomes with those of the 2002-2003 Confidential Enquiry into Maternal and Child Health. METHODS: Existing regional, national and international data sets were compared for content, consistency and validity to develop a standardized data set for diabetes in pregnancy of 46 key clinical items. The data set was tested retrospectively using data from 2007-2008 pregnancies included in three regional audits (Northern, North West and East Anglia). Obstetric and neonatal outcomes of pregnancies resulting in a stillbirth or live birth were compared with those from the same regions during 2002-2003. RESULTS: Details of 1381 pregnancies, 812 (58.9%) in women with Type 1 diabetes and 556 (40.3%) in women with Type 2 diabetes, were available to test the proposed standardized data set. Of the 46 data items proposed, only 16 (34.8%), predominantly the delivery and neonatal items, achieved ≥ 85% completeness. Ethnic group data were available for 746 (54.0%) pregnancies and BMI for 627 (46.5%) pregnancies. Glycaemic control data were most complete-available for 1217 pregnancies (88.1%), during the first trimester. Only 239 women (19.9%) had adequate pregnancy preparation, defined as pre-conception folic acid and first trimester HbA(1c) ≤ 7% (≤ 53 mmol/mol). Serious adverse outcome rates (major malformation and perinatal mortality) were 55/1000 and had not improved since 2002-2003. CONCLUSIONS: A standardized data set for diabetes in pregnancy may improve consistency of data collection and allow for more meaningful evaluation of pregnancy outcomes in women with pregestational diabetes.

Trends in practice of blood glucose control in critically ill patients in the Netherlands.

BACKGROUND: Publication of the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial in 2009 and several observational studies caused a change in the recommendations for blood glucose control in intensive care patients. We evaluated local trends in blood glucose control in intensive care units in the Netherlands before and after the publication of the NICE-SUGAR trial and the revised Surviving Sepsis Campaign (SSC) guidelines in 2012. METHODS: Survey focusing on the timing of changes in thresholds in local guidelines for blood glucose control and interrupted time-series analysis of patients admitted to seven intensive care units in the Netherlands from September 2008 through July 2014. Statistical process control was used to visualise and analyse trends in metrics for blood glucose control in association with the moment changes became effective. RESULTS: Overall, the mean blood glucose level increased and the median percentage of blood glucose levels within the normoglycaemic range and in the hypoglycaemic range decreased, while the relative proportion of hyperglycaemic measurements increased. Changes in metrics were notable after publication of the NICE-SUGAR trial and the SSC guidelines but more frequent after changes in local guidelines; some changes seemed to appear independent of changes in local guidelines. CONCLUSION: Local guidelines for blood glucose practice have changed in intensive care units in the Netherlands since the publication of the NICE-SUGAR trial and the revised SSC guidelines. Trends in the metrics for blood glucose control suggest new, higher target ranges for blood glucose control.

Development of a real-time RT-PCR assay for plasma membrane calcium ATPase isoform 1 (PMCA1) mRNA levels in a human breast epithelial cell line.

The plasma membrane Ca(2+) pump is a key regulator of cytosolic free Ca(2+). Recent studies have demonstrated the dynamic expression of the plasma membrane Ca(2+) pump in a variety of cell types. Furthermore, alterations in plasma membrane calcium pump activity have now been implicated in human disease. In this study, the development of a technique to quantitatively assess mRNA expression of the human plasma membrane Ca(2+) ATPase (PMCA1) isoform of the plasma membrane Ca(2+) pump, using a real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) assay in a human breast epithelial cell line (MCF-7) is described. The sequences of the PMCA1 primers and probe for real-time RT-PCR are presented. The results also indicate that PMCA1 mRNA can be normalized to both 18S ribosomal RNA (18S rRNA) and human glyceraldehyde-3-phosphate dehydrogenase (hGAPDH) in MCF-7 cells. Real-time RT-PCR will be most useful in assessing PMCA1 mRNA expression in cases where only low amounts of RNA are available and/or when numerous samples must be assessed simultaneously.

Disappearance of renin-induced proteinuria by an ACE-inhibitor: a case report.

A 55-year-old man developed renovascular hypertension that was characterized by high plasma renin activity. This was accompanied by nephrotic range proteinuria. Treatment with nifedipine and furosemide lowered the blood pressure to normal values, but proteinuria persisted. However, treatment with an ACE-inhibitor brought resolution of the proteinuria, suggesting a role for angiotensin II in urinary protein loss.

Multi-organ damage in exertional heat stroke.

Exertion-induced heat stroke is a relatively rare disorder in the moderate maritime climate of The Netherlands. Serious complications of excessive physical activity rarely occur. We describe a marathon runner with multi-organ failure after exertion-induced heat stroke. The patient developed shock, diarrhoea, coma, rhabdomyolysis, acute renal failure, liver cell damage and disseminated intravascular coagulation but recovered completely.

[Fatal anaphylactic reaction after oral acetazolamide (diamox) for glaucoma]. / Fatale anafylactische reactie na inname van acetazolamide (Diamox) wegens glaucoom.

A woman aged 66 was prescribed acetazolamide (Diamox) in the outpatient clinic because of glaucoma. She went into irreversible anaphylactic shock with massive pulmonary oedema, probably due to a cross reaction in sulphonamide allergy. Before prescribing acetazolamide, the physician should inquire about sulphonamide allergy because of the related chemical structure of the substances. Such an allergy should be regarded as a contraindication.

[Severe lactic acidosis due to metformin therapy in a patient with contra-indications for metformin]. / Ernstige lactaatacidose bij metforminegebruik bij een patiënt met contra-indicaties voor metformine.

A 52-year-old woman with a medical history of diabetes mellitus type 2, chronic alcoholism and liver function disorders was hospitalized because of complaints of haematemesis, abdominal complaints and dyspnoea. This was due to a severe lactic acidosis caused by acute alcohol intoxication and the use of metformin. With bicarbonate infusion and haemofiltration, the lactic acidosis disappeared, but she developed a distributive shock with multiple organ failure and died 23 days after admission. Lactic acidosis is a rare but serious adverse effect of metformin. Almost all patients described had contraindications to the drug, like renal failure, liver disease, alcohol abuse, and intercurrent conditions causing hypoxia or ischaemia. It is important to be aware of the circumstances in which metformin should not be prescribed.

PMCA1 mRNA expression in rat aortic myocytes: a real-time RT-PCR study.

The plasmalemmal Ca(2+) adenosine triphosphatase (PMCA) is a key regulator of Ca(2+) efflux in vascular smooth muscle. In these studies we developed a real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) assay for assessing PMCA1 mRNA levels in rat primary cultured aortic myocytes. This assay detected fetal bovine serum-induced increases in PMCA1 mRNA (relative to 18S rRNA) 4, 8, and 24 h after stimulation. Early fetal bovine serum-induced increases in PMCA1 mRNA were insensitive to the Ca(2+) channel blockers nifedipine, flunarizine, and SKF-96365. These studies demonstrate the feasibility of real-time RT-PCR to assess mRNA levels of PMCA1 and illustrate dynamic regulation of this Ca(2+) pump isoform in rat primary cultured aortic myocytes.

Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck II.

Pyrrolo[2,3-d]pyrimidines containing a 5-(4-phenoxyphenyl) substituent are novel, potent and selective inhibitors of lck in vitro. Exploration of C-6 position of the pyrrolo[2,3-d]pyrimidine and the terminal phenyl group structure-activity relationship (SAR) is detailed. Compound 1 is orally active in animal models.

Acute effect of ibopamine and isosorbide mononitrate on blood volume distribution in congestive heart failure.

In order to compare ibopamine (IBO), a dopamine congener, with isosorbide mononitrate (ISMN) and to study their interaction in effects on the capacitance vasculature in congestive heart failure (CHF), a prospective, randomized, placebo-controlled, double-blind clinical trial was performed in 32 patients with New York Heart Association class II-IV CHF, randomly assigned to receive single oral doses of placebo, 200 mg IBO, 20 mg ISMN, or both IBO and ISMN. After labelling of red cells with 99mTc, changes in regional radioactivity, indicative of changes in blood volume, were recorded using a gamma-camera before and at 30, 60 and 120 min after drug administration. At 30 and 60 min, arterial systolic and pulse pressures were higher with IBO than with ISMN and placebo (for pulse pressure by mean 13.7 mmHg, 95% confidence interval 4.5-23.0 mmHg, at 30 min), probably reflecting an IBO-induced rise in stroke volume at unchanged heart rate and mean arterial pressure. IBO did not change regional radioactivity except for a transient increase of 4.4% (0.5-7.6%) in the thorax at 30 min. This was attenuated by concomitant ISMN treatment since, starting at 30 min, the drug increased radioactivity in the legs, compared with patients not receiving the drug, by 8.0% (95% confidence interval 0.2-15.8%), leading to a fall in thoracic and left ventricular radioactivity at 30 min of 3.4% (0.3-7.0%) and 6.4% (0.8-11.9%), respectively, and a fall of 5.5% (0.5-10.5%) in hepatic radioactivity at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)