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Biomedical subjects

D Steinke

Publications and source records attributed to D Steinke.

16 recordsLinked to original sources

Eight years' experience of gastrostomy tube management.

BACKGROUND AND STUDY AIMS: Increasingly, patients fed by gastrostomy tube are surviving the lifespan of the device. Data are scarce concerning the factors affecting the longevity and failure of gastrostomy tubes or the criteria for selection of replacement devices which leads to cost-effective patient management. The aims of the study were: to set criteria for selection of replacement gastrostomy tubes; to determine the causes of gastrostomy tube failure, and the factors affecting device longevity; and to examine the effect of initiating an educational programme for caregivers on resource utilization in long-term enteral nutrition patients. MATERIALS AND METHODS: We analyzed the clinical gastrostomy tube database compiled prospectively over 8 years by the nutrition team at Ninewells Hospital, Dundee. RESULTS: For 363 gastrostomy tubes inserted in 304 patients (160 women; median age 71), the median duration of gastrostomy tube use was 138 days. The total follow-up was 294 patient-years. Death occurred before the first gastrostomy tube replacement in 48 % of patients, but 20 % resumed oral nutrition. Tube failure mechanisms were: dislodgment, 28 %; perishing of tube material, 25 %; tube-related Candida albicans infection, 16 %; leakage, 7 %; and unspecified, 7 %. Of the balloon tubes and gastrostomy buttons, 8 % needed early replacement due to dislodgment and/or leakage. The cost per day for replacement percutaneous endoscopic gastrostomy (PEG) was Euro 2.12, for balloon tubes it was Euro 0.62, and for gastrostomy buttons Euro 1.80. Despite an increasing PEG insertion rate throughout the study period, yearly referrals for PEG-related problems dropped by 30 % between 1997 to 1999, coinciding with the initiation of an educational programme for caregivers. CONCLUSION: Tube longevity is mainly limited by the patient's diagnosis and prognosis. The choice of replacement device should be based on clinical factors. The use of more durable materials in the manufacture of gastrostomy tubes may prolong tube life and reduce cost. Education of patients and caregivers by a multidisciplinary nutrition support team promotes independence and limits demand on the service.

Adolescent↗

Association between antibiotic resistance and community prescribing: a critical review of bias and confounding in published studies.

The reported association between antibiotic prescribing and resistance may be subject to bias or confounding. Bias describes any effect at any stage of investigation or inference tending to produce results that depart systematically from the true value. A confounding variable is one that is associated independently with both exposure and outcome. Confounding variables may create an apparent association or mask a real association. Pharmacoepidemiology is the study of the use and the effects of drugs in large numbers of people. We have used standard pharmacoepidemiological methods to investigate sources of bias and confounding in the association between prescribing and resistance. We conclude that the association is statistically valid and that the consistency of evidence supports a cause-effect relationship. Nonetheless, several important sources of bias and confounding must be taken into account in future studies that analyze the impact of prescribing policies on resistance.

Anti-Bacterial Agents↗

Not so simple cystitis: how should prescribers be supported to make informed decisions about the increasing prevalence of infections caused by drug-resistant bacteria?

Trimethoprim is a safe, effective, and inexpensive treatment for cystitis. However, at least 25% of bacteria isolated from urine samples in general practice are now resistant to trimethoprim in the laboratory. The relationship between laboratory resistance and clinical outcome is complex. Cephalexin appears to be more active than trimethoprim in the laboratory but has been consistently less effective in clinical trials. There is little point in collecting data about the prevalence of drug resistance in urinary bacteria unless it is linked to evidence about the impact of resistance on clinical outcomes. Pragmatic clinical trials are required to provide practices with clear thresholds for managing their antibiotic policies; for example, 'Change from trimethoprim to drug X when the probability of trimethoprim resistance reaches Y%.' Prescribers should be aware that trimethoprim resistance is most likely to occur in patients who have been exposed to trimethoprim or other antibiotics in the previous six months, and that the risk increases with age. This information could be used to stratify women according to risk of infection by trimethoprim-resistant bacteria. Health education leaflets are an effective method for reducing the frequency of recurrent cystitis. Symptomatic treatment can control symptoms and allow time for microbiological investigation. Both of these strategies may help to reduce unnecessary prescribing of antibiotics in general and quinolones in particular.

Adult↗

Diabetes and lower-limb amputations in the community. A retrospective cohort study. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland/Medicines Monitoring Unit.

OBJECTIVE: There are few U.K. data on the incidence rates of amputation in diabetic subjects compared with the nondiabetic population. RESEARCH DESIGN AND METHODS: We performed a historical cohort study of first lower-extremity amputations based in Tayside, Scotland (population 364,880) from 1 January 1993 to 31 December 1994. The Diabetes Audit and Research in Tayside Scotland (DARTS) database was used to identify a prevalence cohort of 7,079 diabetic patients on 1 January 1993. We estimated age-specific and standardized incidence rates of lower-limb amputations in the diabetic and nondiabetic cohorts. Results were compared with a previous study that evaluated lower-extremity amputations in diabetic patients in Tayside in 1980-1982. RESULTS: There were 221 subjects who underwent a total of 258 nontraumatic amputations. Of the 221 subjects, 60 (27%) patients were diabetic (93% NIDDM), and 63% were first amputations. The median duration of diabetes was 6 years (range: newly diagnosed to 41 years). Nonhealing ulceration (31%) and gangrene (29%) were the two main indications for amputation in the diabetic subjects. Of the 161 nondiabetic subjects, 140 (80%) underwent first amputations. The adjusted incidences in the diabetic and nondiabetic groups were 248 and 20 per 100,000 person-years, respectively. Tayside patients with diabetes thus had a 12.3-fold risk of an amputation compared with nondiabetic residents (95% CI 8.6-17.5). The estimated proportion of diabetic patients in the population rose from 0.81% in 1980-1982 to 1.94% in 1993-1994, whereas the absolute rate of amputation in diabetic subjects was unchanged from that in 1980-1982. CONCLUSIONS: These population-based U.K. amputation data are similar to amputation rates in the U.S. Amputation rates appear to have decreased significantly since 1980-1982. The impact of diabetes education and prevention programs that target the processes leading to amputation can now be evaluated.

Adolescent↗

Formation of peptide bonds by carboxypeptidase c from orange leaves.

Carboxypeptidase c partially purified from orange leaves was studied as a catalyst for enzymatic peptide synthesis. Various N-protected ester- and nucleophile compounds were evaluated in order to determine the substrate specificity. For further characterization of the synthetic reaction, optimum pH and the influence of the N-terminal protecting group were studied. Kinetic investigations revealed considerable differences in Km and Vmax for the nucleophile when the N-terminal protecting group of the substrate was varied.

Amino Acid Sequence↗

Influence of water miscible organic solvents on orange flavedo peptide amidase.

Due to the broad substrate spectrum and stability in some water-miscible organic solvents, the peptide amidase from orange flavedo was found to be a suitable enzyme for experiments in water-miscible organic solvents. Immobilization and the kind of organic solvent had no significant influence on the kinetic data while the polarity of the substrate caused a great difference in the apparent Km values. The results are explained by inadequate partition of the substrate between the microenvironment of the enzyme and the reaction solution.

Amidohydrolases↗

Application of carboxypeptidase C for peptide synthesis.

Carboxypeptidase C partially purified from the flavedo of citrus fruit by a new, simple procedure was studied as a catalyst for peptide-bond formation. Dipeptides were obtained in high yields (80-95%) with Bz--Tyr--OEt as carboxyl-compound, and amino acid amides and amino acid alkylesters as nucleophiles. To characterize the synthesis reaction, a number of parameters such as pH, excess of the nucleophile, and the molarity of the buffer were evaluated. The yield of dipeptides depends on the side chain of the amino acid alkylester used as the carboxyl component as well as on the N-terminal protecting group. Esterase activity was minimal in the absence of a nucleophile, suggesting a modified mechanism for the synthesis reaction compared to other serine proteases. No secondary hydrolysis of the peptides formed was observed.

Carboxypeptidases↗

Optimization of enzyme-mediated peptide bond formation.

Enzyme-catalyzed peptide bond formation requires thorough examination and optimization of each coupling step. In order to identify factors influencing the selectivity between aminolysis and hydrolysis, a systematic study was carried out for the kinetically controlled peptide synthesis. The reaction temperature, the type of C-terminal protecting group, and different organic cosolvents showed little influence on the selectivity. The enzyme, excess nucleophile, pH, N-terminal protecting group, and ionic strength of the solution were identified as major factors controlling the selectivity and, therefore, the yield of the dipeptide synthesis. Under optimized conditions, the selectivity of the chymotrypsin-catalyzed synthesis of PheSer could be increased from 35 to 100%.

Carboxypeptidases↗

Effect of intrathecal thrombolytic therapy on subarachnoid clot and chronic vasospasm in a primate model of SAH.

The safety and efficacy of the thrombolytic agent tissue-type plasminogen activator (tPA) in the elimination of subarachnoid clot and prevention of chronic vasospasm were evaluated in a blind randomized placebo-controlled trial. Twenty-four monkeys were randomly assigned to one of two groups of 12. Each group underwent baseline cerebral angiography and coagulation analysis followed by right-sided craniectomy and experimental subarachnoid hemorrhage (SAH). An Ommaya reservoir was inserted with its catheter placed into the subarachnoid space. Twenty-four hours later one group (the tPA group) received 0.5 mg of tPA in 0.5 ml of buffer injected into the reservoir every 8 hours for three doses, while the second group (the placebo group) received the same volume of normal saline. On Day 7, angiography was repeated and the animals were sacrificed. One animal from the placebo group developed a delayed ischemic neurological deficit on Day 5 after SAH. Moderate to severe vasospasm (greater than 30% reduction in vessel caliber) was present on Day 7 in the internal carotid and middle cerebral arteries of the animals in the placebo group (p less than 0.01), while in the tPA group only mild narrowing of the anterior cerebral artery was seen. No significant change in coagulation status occurred in either group. All animals in the placebo group had a large amount of subarachnoid clot remaining at the time of sacrifice, but 11 of the 12 animals in the tPA group were completely free of clot. The results of electron microscopic studies of the cerebral arteries correlated with angiography, and there was no histological evidence of brain inflammation associated with the intrathecal use of tPA.

Animals↗

Hydrocephalus following aneurysmal subarachnoid haemorrhage.

Ninety-four patients with hydrocephalus following subarachnoid haemorrhage were investigated. Fourteen of these patients had temporary ventricular drains inserted, 19 had drains that were later converted to ventricular-peritoneal shunts, and 61 patients had shunts only. All patients were analysed with respect to their grade on admission, the distribution of blood on CT scan, their Glasgow Coma Score, their intracranial pressure, and the presence or absence of vasospasm on angiography. Outcome was analysed by shunt procedure and time of shunt insertion. The higher the grade on admission, the more likely it was the patient would require a shunt. Fewer patients with a good outcome required shunting as compared to those whose outcome was poor. Patients having more subarachnoid blood on CT scan tended to present with a lower Glasgow Coma Score. The outcome of patients with intraventricular haemorrhage was not obviously influenced by the insertion of a ventriculostomy. Vasospasm was not more common in patients requiring a ventriculo-peritoneal shunt, nor did early shunting in patients with hydrocephalus affect the incidence of vasospasm. The majority of patients were either shunted in the first three days or after 30 days post-SAH. The outcome was better in those patients shunted at a later date.

Acute Disease↗

The multiple propensity score for analysis of dose-response relationships in drug safety studies.

In order to detect adverse drug reactions, large observational drug safety studies are necessary as randomized clinical trials rarely have enough power. However, in order to obtain reliable results the issue of confounding, especially confounding by indication, should be addressed. We proposed a multiple propensity score, which is an extension of the propensity score, to reduce the bias in a dose-response analysis in a drug safety study. The multiple propensity score has similar properties to the propensity score in Rosenbaum and Rubin.(1) Using the propensity score for bias reduction of the risk ratio was considered. We used the multiple propensity score in a study of the dose-response relationship between diclofenac prescriptions and hospitalization for gastrointestinal bleeding and perforation using a record linkage database. We found that the unadjusted risk ratios were biased downwards due to confounders and that this bias was reduced by using stratification based on the multiple propensity score.

Adult↗