PubMed Health⌕ Search

Biomedical subjects

Malcolm G Coulthard

Publications and source records attributed to Malcolm G Coulthard.

15 recordsLinked to original sources
PubMed2006

Quantifying how tests reduce diagnostic uncertainty.

BACKGROUND: Diagnostic tests are commonly evaluated from sensitivity and specificity, which are robust and independent of prevalence, but clinically not intuitive. Many clinicians prefer to use positive and negative predictive values (PPV and NPV), but they are frequently applied as if they are independent of prevalence, whereas this may make an important difference. METHODS AND RESULTS: We present graphs that allow easy reference to appropriate values and demonstrate that PPV and NPV are not independent of prevalence. PPV and NPV figures reflect the prior probability of the case having a positive diagnosis, estimated clinically from the history, examination and other results, as well as the impact of the test result. To avoid the common error of allowing for prior probability twice, and to interpret the impact of the test result alone, we present graphs of the proportionate reduction in uncertainty score (PRU), calculated from sensitivity, specificity and prevalence. These plots show the extent to which either a positive or negative test result affects the remaining degree of uncertainty about a diagnosis in either direction, according to likely clinical prevalence. CONCLUSIONS: PRU plots demonstrate the discriminatory value of tests more clearly than sensitivity and specificity from which they are derived, and should be published alongside them.

Child↗
PubMed2006

Comparison of alteplase and heparin in maintaining the patency of paediatric central venous haemodialysis lines: a randomised controlled trial.

OBJECTIVES: To determine whether the tissue plasminogen activator, alteplase, is more effective than heparin in preventing blood clots developing in children's haemodialysis central lines between dialysis sessions. DESIGN: A prospective double-blind, within-patient multiperiod cross-over controlled trial of instilling a "lock" of either heparin 5000 U/ml or alteplase 1 mg/ml into the central lines of two children haemodialysed twice weekly, and seven dialysed thrice weekly, over 10 weeks. SETTING: A UK paediatric nephrology unit. MAIN OUTCOME MEASURES: Weight of blood clot aspirated from the line at the start of the next dialysis session. RESULTS: The odds of a clot forming was 2.4 times greater with heparin than alteplase (95% CI 1.4 to 4.0; p = 0.001), and when present they were 1.9 times heavier (31 vs 15 mg; 95% CI 1.5 to 2.4; p<0.0005). There was no effect of inter-dialytic interval. One child required an alteplase infusion to clear a blocked line following a heparin lock. We subsequently changed our routine locks from heparin to alteplase. Comparing the year before and after that change, the incidence of blocked lines requiring an alteplase or urokinase infusion fell from 2.7 to 1.2 per child (p<0.03), and the need for surgical replacements from 0.7 to nil (p<0.02). CONCLUSION: Alteplase is significantly more effective than heparin in preventing clot formation in central haemodialysis lines. This reduces morbidity and improves preservation of central venous access. It is more expensive, though relatively economic if packaged into syringes and stored frozen until needed, but reduces the costs of unblocking or replacing clotted lines.

Catheterization, Central Venous↗
PubMed2006

Should paediatric central lines be aspirated before use?

As blood clots commonly occur in the lumens of paediatric haemodialysis central-venous lines, they must be routinely aspirated before use to prevent pulmonary emboli. The smaller diameter lines used for parenteral nutrition and cancer chemotherapy are seldom managed this way. We looked for clots formed when children undergoing cancer chemotherapy had their heparin-locked central lines accessed, and compared with the lines of children undergoing haemodialysis. Patients undergoing haemodialysis had clots aspirated on 83% of occasions, and each child had clots at least once. Clots also occurred in the smaller lines, but they were less frequent (64%, p = 0.01), and had a lower median weight than those in dialysis lines (14.1 v 25.2 mg, p = 0.01). When small diameter central lines are used without initial aspiration, small pulmonary emboli are likely to occur, but are unlikely to be individually clinically important. Daily use, as with long-term parenteral nutrition, might result in >3 g of clot being embolised annually. Consideration should be given to aspirating all paediatric central lines before use.

Antineoplastic Agents↗
PubMed2006

Renovascular hypertension commencing during fetal life.

We report three infants with severe, early hypertension due to unilateral renovascular disease, whose cardiovascular changes, or polycythaemia, or both, indicated they had been affected as fetuses. All underwent unilateral nephrectomy, and had a similar histology, with patchy areas having relatively normal glomeruli but immature proximal tubules. This pattern may be a marker for renovascular disease in fetal life.

Female↗
PubMed2006

Follow-up of early unilateral nephrectomy for hypertension.

Early unilateral nephrectomy was carried out in four young children with unilateral renovascular disease, a poorly functioning kidney and hypertension. At follow-up 5-16 years later all showed normal growth, blood pressure and renal function, and only one child had low-grade albuminuria. Unilateral nephrectomy seems to be a safe and effective alternative to long-term hypotensive treatment.

Blood Pressure↗
PubMed2006

Reflux nephropathy in kidney transplants, demonstrated by dimercaptosuccinic acid scanning.

BACKGROUND: This study determines why kidney transplants develop new focal defects. METHODS: Thirty children at a U.K. pediatric nephrology department receiving kidney transplants had early and late dimercaptosuccinic acid (DMSA) scans to detect acquired focal defects, and their presence correlated with possible risk factors. Associations between clinical events and focal DMSA lesions appearing in grafts were measured. RESULTS: Of the 30 early DMSA scans (within 2 weeks of function), one child with a thrombosed polar artery had a focal defect. On rescanning later, 11 (37%) had acquired segmental defects; five were multiple, and their glomerular filtration rates were 20 ml/min/1.73 m lower (95% CI 7-34). Histology in one case showed pyelonephritic scarring. Reflux into the transplant ureter occurred in 19/27 (70%) of children tested (by radiological or indirect radionuclide cystography). Nine of 13 children (69%) who had a combination of reflux and a urine infection had acquired scars, whereas only 1/14 (7%) did without this combination (P = 0.001). Scarring was not associated with the age or sex of the donor or recipient, rejection episodes, renal biopsy, or drug-induced nephrotoxicity. CONCLUSION: Kidney transplants are at high risk of developing segmental pyelonephritic scars if infected urine refluxes into the graft, either early through a transanastomotic stent or later from vesicoureteric reflux. These scars may reduce the renal function and are readily seen on DMSA, but not ultrasound scans. Consideration should be given to more effective antireflux surgery for transplants, with subsequent testing for reflux, urinary antibiotic prophylaxis, and prompt treatment of urine infections.

Adolescent↗
PubMed2006

Acute appendicitis occurring immediately post-renal transplant.

A 10-yr-old boy who presented with vomiting and abdominal pain 12 days after an uneventful renal transplant had no identifiable transplant-related cause for these symptoms. Four days later a perforated appendix was diagnosed. His case illustrates that common abdominal pathologies may present differently in immunosuppressed, transplanted patients, causing diagnostic delay.

Acute Disease↗
PubMed2005

A machine for haemodialysing very small infants.

Babies weighing under 6 kg are difficult to dialyse, especially those as small as 1 kg. Peritoneal dialysis is easier than haemodialysis, but is not always possible, and clears molecules less efficiently. Two factors complicate haemodialysis. First, extracorporeal circuits are large relative to a baby's blood volume, necessitating priming with fresh or modified blood. Second, blood flow from infants' access vessels is disproportionately low (Poiseuille's law), causing inadequate dialysis, or clotting within the circuit. These problems are minimised by using single lumen access, a very small circuit, and a reservoir syringe to separate the sampling and dialyser blood flow rates. Its manual operation is tedious, so we developed a computer-controlled, pressure-monitored machine to run it, including adjusting the blood withdrawal rate from poorly sampling lines. We have dialysed four babies weighing 0.8-3.4 kg, with renal failure or metabolic disorders. The circuits did not require priming. Clearances of creatinine, urea, potassium, phosphate and ammonia were mean (SD) 0.54 (0.22) ml/min using one dialyser, and 0.98 (0.22) ml/min using two in parallel. Ammonia clearance in a 2.4 kg baby had a 9 h half-life. Ultrafiltration up to 45 ml/h was achieved easily. This device provided infants with immediate, effective and convenient haemodialysis, typically delivered for prolonged periods.

Body Size↗
PubMed2003

A nurse led education and direct access service for the management of urinary tract infections in children: prospective controlled trial.

OBJECTIVES: To determine whether a nurse led education and direct access service improves the care of children with urinary tract infections. DESIGN: Prospective cluster randomised trial. SETTING: General practitioners in the catchment area of a UK paediatric nephrology department. PARTICIPANTS: 88 general practices (346 general practitioners, 107 000 children). MAIN OUTCOME MEASURES: Rate and quality of diagnosis of urinary tract infection, use of prophylactic antibiotics, convenience for families, and the number of infants with vesicoureteric reflux in whom renal scarring may have been prevented. RESULTS: The study practices diagnosed twice as many urinary tract infections as the control practices (6.42 v 3.45/1000 children/year; ratio 1.86, 95% confidence interval 1.42 to 2.44); nearly four times more in infants (age < 1 year) and six times more in children without specific symptoms. Diagnoses were made more robustly by study practices than by control practices; 99% v 89% of referred patients had their urine cultured and 79% v 60% had bacteriologically proved urinary tract infections (P < 0.001 for both). Overall, 294 of 312 (94%) children aged under 4 years were prescribed antibiotic prophylaxis by study doctors compared with 61 of 147 (41%) by control doctors (P < 0.001). Study families visited hospital half as much as the control families. Twice as many renal scars were identified in patients attending the study practices. Twelve study infants but no control infants had reflux without scarring. CONCLUSION: A nurse led intervention improved the management of urinary tract infections in children, was valued by doctors and parents, and may have prevented some renal scarring.

Anti-Bacterial Agents↗
PubMed2002

Do kidneys outgrow the risk of reflux nephropathy?

Three-quarters of human kidneys have segments that will allow intrarenal reflux if the person is one of the 1% that is also born with vesicoureteric reflux (VUR). It is likely that entry of infected urine into these segments produces permanent damage within just a few days, as it does in piglets and adult pigs. This very rapid course leaves no time for delay in diagnosing and treating urine infections in infants, the group that present the greatest clinical difficulties. It is proposed that the reason why the risk of scarring starts off high and falls to virtually nil by 4 years is not due to maturation that leads to an increased resistance to scarring, but because most vulnerable subjects have already scarred their kidneys in infancy. This proposed model has important implications for clinical management. First, it suggests that current practice identifies scars in children due to urine infection, but prevents few. Second, babies known to have VUR from birth, and protected from scarring with prophylactic antibiotics, will not outgrow their scarring risk by any particular age, but will remain at risk until they outgrow their reflux. This suggests their kidneys need to be protected from scarring until then, perhaps by antibiotic prophylaxis. Third, transplant recipients of any age with refluxing ureteric anastamoses or stents will carry a risk of developing a focal scar if they acquire a urine infection, and may need protection.

Animals↗
PubMed2002

Renal scarring caused by vesicoureteric reflux and urinary infection: a study in pigs.

The diminishing risk of acute renal scarring with urine infections (reflux nephropathy) after infancy is unexplained, but might reflect kidney maturation. The mechanisms of reflux nephropathy scarring are best explained by a piglet model in which vesicoureteric reflux allows infected urine to enter those segments of renal parenchyme that are drained by compound papillae. We carried out a similar study in adult pigs to determine whether protective maturation occurs. Adult pigs were exposed to urine infection after surgery to produce unilateral vesicoureteric reflux. The intravesical portion of one ureter was deroofed in six female adult Gottingen mini-pigs and the bladder and the ureteric mucosae stitched around the perimeter of the new orifice. One week later Escherichia coli was injected into the urinary bladder to produce cystitis. Three weeks later the animals were killed humanely and the urinary tracts were examined. The animals sustained persistent urine infections; the untreated ureters and kidneys remained normal. However, on the operated side, the ureters were thickened and dilated, vesicoureteric reflux was shown in four cases, and the kidneys had one or more flattened area overlying a renal segment, which showed severe inflammatory changes and early scar formation. The risk of reflux nephropathy scarring is not eliminated by maturation of the kidney in pigs. It is unlikely that the much-reduced risk of initiating scarring that is seen in older children with urine infections is due to a protective maturation of the human kidney. A possible explanation is that most children born with risk factors for developing scarring will have already sustained scars when very young.

Age Factors↗
PubMed2002

Reflux nephropathy in transplants.

Reflux nephropathy, renal scarring after urine infection, typically occurs in infancy. Although vesicoureteric reflux occurs commonly in kidney allografts, grafts have not previously been regarded as likely to be affected by reflux nephropathy, perhaps because older kidneys are considered to have matured out of the risk. Evidence that adult pigs remain at risk of reflux nephropathy challenges that assumption. We therefore reviewed the pathological findings in allograft nephrectomy specimens to look for evidence of reflux nephropathy, and sought evidence of focal transplant renal scarring in paediatric recipients who had a urine infection and vesicoureteric reflux. Consecutive allograft nephrectomy specimens (146) that had been removed between 1990 and 1999 were examined for evidence of reflux nephropathy, and relevant case notes were reviewed. Also, children with a renal transplant who had a urine infection were investigated for focal scarring by dimercaptosuccinic acid (DMSA) scanning and for reflux with a cystogram. Four transplanted kidneys from adult donors that were removed from adult recipients had developed changes consistent with reflux nephropathy. Of these, 3 also had definite evidence and 1 probable evidence of a glomerulopathy associated with hyperfiltration due to reduced renal mass. All 4 patients had had recurrent urine infection and the 2 assessed had had vesicoureteric reflux. Two children with renal transplants that also had urine infections and vesicoureteric reflux to their graft were shown to have sustained focal damage on DMSA scan, confirmed as reflux nephropathy scarring on biopsy in 1 case. The grafts were aged 14.4 years and over 16 years at the time of scarring. Reflux nephropathy can occur in previously healthy adult human kidneys after transplantation. Previous studies of the effect of vesicoureteric reflux on renal allografts were not designed to assess the possibility of mild or focal scarring.

Adolescent↗