bluuebunny/crossref_metadata_2025 huggingface dataset:
Charge carrier transport in poly[methyl(phenyl)silylene]: the effect of additives
Authors: Nešpůrek S. , Valerián H. , Eckhardt A. , Herden V. , Schnabel W.
Published: August 2002

Poly[methyl(phenyl)silylene], PMPSi, was doped with compounds of the electron acceptor type. The charge carrier mobility increases with increasing electron affinity of the acceptors having zero dipole moments. At the same time the energy distribution of hopping states narrows. On the other hand, the hole drift mobility is influenced by the dipole moment of the dopand. The electrostatic charge carrier‐dipole interaction causes a broadening of the energy distribution of transport states which results in a decrease in the charge carrier mobility. The charge carrier transport can be explained by the disordered polaronic theory, according to which the activation energy of charge carrier mobility has contributions based on the dynamic disorder, i.e. the polaronic barrier, and on the static disorder, i.e. the variation of the energy of transport states as a result of the environment. Copyright © 2001 John Wiley & Sons, Ltd.
Direct analysis of single leaf disks for chemopreventive glucosinolates
Authors: Wang Qiaomei , Grubb C. Douglas , Abel Steffen
Published: August 2002

Natural isothiocyanates, produced during plant tissue damage from methionine‐derived glucosinolates, are potent inducers of mammalian phase 2 detoxification enzymes such as quinone reductase (QR). A greatly simplified bioassay for glucosinolates based on induction and colorimetric detection of QR activity in murine hepatoma cells is described. It is demonstrated that excised leaf disks of Arabidopsis thaliana (ecotype Columbia) can directly and reproducibly substitute for cell‐free leaf extracts as inducers of murine QR, which reduces sample preparation to a minimum and maximizes throughput. A comparison of 1 and 3 mm diameter leaf disks indicated that QR inducer potency was proportional to disk circumference (extent of tissue damage) rather than to area. When compared to the QR inducer potency of the corresponding amount of extract, 1 mm leaf disks were equally effective, whereas 3 mm disks were 70% as potent. The QR inducer potency of leaf disks correlated positively with the content of methionine‐derived glucosinolates, as shown by the analysis of wild‐type plants and mutant lines with lower or higher glucosinolate content. Thus, the microtitre plate‐based assay of single leaf disks provides a robust and inexpensive visual method for rapidly screening large numbers of plants in mapping populations or mutant collections and may be applicable to other glucosinolate‐producing species. Copyright © 2002 John Wiley & Sons, Ltd.
Second‐trimester maternal serum alpha‐fetoprotein (MSAFP) iselevated in women with adverse pregnancy outcome associated with inherited thrombophilias
Authors: Ochshorn Yifat , Kupferminc Michael J. , Eldor Amiram , Wolman Igal , Lessing Joseph B. , Yaron Yuval
Published: August 2002

Obstetric complications, such as severe pre‐eclampsia, fetal growth restriction, abruptio placentae, or stillbirth are associated with abnormally elevated second‐trimester maternal serum alpha‐fetoprotein (MSAFP) and β subunit of human chorionic gonadotrophin (βhCG). This has been attributed to placental abnormalities. Women with thrombophilias have been shown to have abnormalities of the placenta resulting in adverse pregnancy outcome in these patients. The purpose of the present study was to evaluate whether women with pregnancy complications and inherited thrombophilias have abnormally elevated second‐trimester MSAFP or βhCG. Sixty‐two women with pregnancy complications were tested for inherited thrombophilias several months after delivery. The thrombophilia group included 29 women with pregnancy complications and an inherited thrombophilia and the control group included 33 other patients without thrombophilia. Patients in the thrombophilia group had a higher median MoM MSAFP compared to the controls (1.337 vs 1.086, p=0.0516). The incidence of abnormally elevated MSAFP (>2.5 MoM) was also significantly higher in the thrombophilia group compared to controls (21% vs 3%, p=0.04). Neither the median MoM βhCG nor the incidence of abnormally elevated βhCG were significantly different between the groups. We conclude that second trimester MSAFP, but not βhCG, is abnormally elevated in patients with thrombophilia and obstetric complications. Copyright © 2001 John Wiley & Sons, Ltd.
Measurement of inhibin A: a modification to an enzyme‐linked immunosorbent assay
Authors: Thirunavukarasu Prema P. , Wallace Euan M.
Published: August 2002

Inhibin A is a useful prenatal marker of Down syndrome. Currently, the available enzyme‐linked immunosorbent assays (ELISAs) for inhibin A are based upon the same paired monoclonal antibodies. In the present study we have confirmed for one of those ELISAs that short‐term sample storage as whole blood leads to a significant decline in detectable inhibin A and that this is most likely due to erythrocyte catalase interference with a critical oxidation step in the assay. While this interference can be eliminated by heating the samples pre‐assay, this process is labour intensive. In the present study we have demonstrated that the addition of 3‐amino‐1,2,4‐triazole (AT), a catalase ‘suicide’ inhibitor, also prevents the decline of inhibin A levels in samples stored as whole blood. We suggest that the addition of AT to samples prior to assay is a simple modification to the inhibin A ELISA that affords optimum performance. Copyright © 2001 John Wiley & Sons, Ltd.
Prenatal diagnosis of ATR‐X syndrome in a fetus with a new G>T splicing mutation in the XNP/ATR‐X gene
Authors: Fichera Marco , Silengo Margherita , Spalletta Angela , Lo Giudice Mariangela , Romano Corrado , Ragusa Angela
Published: August 2002

The molecular cause of the α‐thalassemia/mental retardation syndrome (ATR‐X) resides in mutations affecting the XNP/ATR‐X gene. Recently molecular defects in the gene have been found in singular cases of a discrete number of X‐linked mental retardation (XLMR). ATR‐X‐affected males are characterised by severe mental retardation, distinct facial dysmorphisms and genital abnormalities, besides a wide spectrum of pathological features and an extremely limited biological fitness. Given that molecular investigation of XNP/ATR‐X mutations is made onerous by the length of the gene transcript, we carried out a prenatal diagnosis in a fetus at risk for ATR‐X syndrome by initially determining the XNP/ATR‐X gene haplotype before considering gene sequencing. Disease‐associated haplotype analysis was performed selecting five genic (CA)n repeats that showed high heterozygosity (Het>0.7) in the general population. The fetus segregated an identical allelic pattern to that of the affected child of the family under investigation who shows features suggestive of the ATR‐X syndrome. Subsequent mutational analysis of the gene revealed a novel IVS3+1G>T splicing mutation confirming the diagnosis. Copyright © 2001 John Wiley & Sons, Ltd.
Karyotype, phenotype and parental origin in 19 cases of triploidy
Authors: Daniel Art , Wu Zhanhe , Bennetts Bruce , Slater Howard , Osborn Robert , Jackson Julianne , Pupko Vladimir , Nelson John , Watson Geoff , Cooke‐Yarborough Claire , Loo Christine
Published: August 2002

The parental origin of triploidy in 19 cases was examined by inheritance of DNA microsatellites and by methylation patterns of SNRPN or PW71 (where parents' blood was unavailable). The fetal and placental morphology on these cases was reviewed. The phenotype of the fetuses with non‐mosaic triploidy was assessed in relation to the two types described by McFadden and Kalousek. Of the diandric fetuses three of the six showed mild‐to‐moderate symmetrical growth retardation and the other three had growth characteristics in accordance with their gestational ages. This study would suggest the fetal triploid ‘Type 1’ definition be modified to ‘well grown to moderate symmetrical IUGR’ to allow for such variation. In the digynic fetuses (McFadden/Kalousek Type 2) there were poor growth characteristics with IUGR being more severe and asymmetrical. The diandric fetuses were as common as digynic fetuses in this series. The ratio of diandric to digynic specimens was 11:8 but if only fetal specimens (not embryos or mosaic children) were included the ratio was 6:5. Many diandric conceptions end as partial moles but later in gestation diandric fetuses may be well grown. It is proposed that there may be a survival barrier for diandric fetuses early in gestation (possibly based on the proportion of vascularised placental villi), although once this is passed the diandric fetuses are comparatively more viable and better grown than digynic fetuses. In the XXY triploid fetuses, 5/6 had hypoplastic or ambiguous external genitalia (two were recorded as of female phenotype) as has been reported previously. In these, the gonadal histology was testicular in all the diandrics but in the single digynic XXY case, sex reversal was complete with normal uterus and Fallopian tubes and the gonads were histologically ovaries. Two triploid/diploid mosaics were proven to be due to digyny. The probable cause is delayed incorporation of the second polar body into a blastomere and there was evidence of identical alleles from the same sperm being present in both diploid and triploid cells. In one of these triploid/diploid mosaics in which there was a termination of pregnancy (TOP) after prenatal karyotyping the diploid cell line had trisomy 16 which was not evident in the triploid line. This trisomy was probably of post‐zygotic origin and we suggest the fetus was rescued by the prominence of the triploid line. Copyright © 2001 John Wiley & Sons, Ltd.
Preimplantation genetic diagnosis of pericentric inversions
Authors: Escudero Tomás , Lee Michael , Stevens John , Sandalinas Mireia , Munné Santiago
Published: August 2002

Inversions are structural chromosome abnormalities that may be associated with infertility, multiple miscarriage and chromosomally unbalanced offspring. Preimplantation genetic diagnosis (PGD) with subtelomeric probes was used to select for transfer only those embryos that were normal or balanced for three pericentric inversions. In contrast to previous protocols the present procedure allows the detection of unbalanced embryos that might arise from U‐recombination in the inverted region. Additionally, aneuploidy screening was carried out in two cases by a second round of fluorescent in situ hybridization (FISH) with centromeric probes. Of the three couples that underwent the procedure one became pregnant twice. The first pregnancy delivered a healthy and chromosomally normal baby and the second pregnancy is ongoing with triplets. Copyright © 2001 John Wiley & Sons, Ltd.
Duplication of chromosome 2 in association with ventriculomegaly — a case report
Authors: Martin W. L. , Pretlove S. , Mercer A. , Platt C. C. , Roberts E. , Davison V. , Kilby M. D.
Published: August 2002

This is a case report of the prenatal diagnosis of a de novo interstitial duplication of chromosome 2 (46,XX,dup(2)(p13p21) de novo) with an associated phenotypic abnormality. This chromosomal duplication is rare, only one has previously been described prenatally. Postnatal reports of similar duplications in this region have described associated dysmorphic features and significant neurodevelopmental delay. In our case, the only ultrasound finding was moderately severe ventriculomegaly. At post‐mortem, ventriculomegaly was confirmed and there was associated macrocephaly (head circumference above the 97th centile) with no dysmorphic features seen. Copyright © 2001 John Wiley & Sons, Ltd.
Improvement of mesenteric superior artery Doppler velocimetry by amnio‐infusion in fetal gastroschisis†
Authors: Volumenie Jean‐Luc , de Lagausie Pascal , Guibourdenche Jean , Oury Jean‐François , Vuillard Edith , Saizou Carole , Luton Dominique
Published: August 2002

This study aimed to analyse the influence of amnio‐infusion on superior mesenteric Doppler velocimetry and to correlate Doppler data with outcome in fetuses presenting with gastroschisis. Umbilical and intra‐ and extra‐abdominal superior mesenteric artery Doppler velocimetry was measured prospectively before and after amnio‐infusion in fetuses with gastroschisis. Doppler index values and changes were correlated with the following outcome parameters: importance of fibrous coating, duration of hospitalization in the neonatal intensive care unit, total duration of hospitalization, duration of parenteral feeding, duration of ventilatory assistance, and the interval to initiation of oral feeding. A significant improvement of diastolic flow was observed in the extra‐abdominal superior mesenteric artery with amnio‐infusion. No similar change was seen in the intra‐abdominal superior mesenteric or in the umbilical artery. Pre‐amnioinfusion extra‐abdominal mesenteric Doppler index was correlated with maximal diameter of exteriorized bowel and slightly with duration of hospitalization in the neonatal intensive care unit, but no other relation between Doppler index and outcome parameter could be ascertained. Amnio‐infusion induces modifications in the vascularization of exteriorized bowel in gastroschisis. This could partly explain the beneficial effect of this procedure on fetal gut. Copyright © 2001 John Wiley & Sons, Ltd.
AZFc deletion detected in a newborn with prenatally diagnosed Yq deletion
Authors: Tóth András , Tardy Erika P. , Gombos Sándor , Hajdu Krisztina , Bátorfi József , Krausz Csilla
Published: August 2002

A case of prenatally diagnosed Yq deletion is described. Fluorescence in situ hybridisation (FISH) was used to identify the abnormal chromosome and to exclude mosaicism. Based on the cytogenetic result and the ultrasound investigation the pregnancy was continued. A newborn with normal male genitalia was delivered. Microdeletion analysis of the Yq showed the absence of the AZFc region. This type of deletion has been described as being associated with azoospermia or oligozoospermia with a progressive decrease of sperm number over time. Long‐term andrological follow‐up of the newborn will be necessary with eventual cryoconservation of sperm at early adulthood. The present report proposes that AZF analysis combined with FISH has an important role in accurate genetic counselling in sex chromosome anomalies. Copyright © 2001 John Wiley & Sons, Ltd.
Prenatal evaluation of fetal neck masses in preparation for the EXIT procedure: the value of pulmonary Doppler ultrasonography (PDU)
Authors: Kalache Karim D. , Masturzo Bianca , Pierro Agostino , Peebles Donald , Chitty Lyn S.
Published: August 2002

Sonographic demonstration of normal tracheal diameter and breathing‐related lung fluid flow at 30 weeks' gestation in a fetus with a giant neck mass confirmed patent airways, thus avoiding an EXIT procedure. Copyright © 2001 John Wiley & Sons, Ltd.
Role of amniotic fluid interphase fluorescence in situ hybridization (FISH) analysis in patient management
Authors: Cheong Leung Wing , Chitayat David , Seaward Gareth , Windrim Rory , Ryan Greg , Barrett Jon , Winsor Elizabeth J. T.
Published: August 2002

We retrospectively reviewed 309 amniotic fluid interphase fluorescence in situ hybridization (FISH) analyses performed from October 1995 to June 1999 to assess the role of interphase FISH in the management of patients at increased risk for fetal aneuploidies. Gestational age and indications for amniocentesis, clinical interventions after FISH results, as well as interventions after final culture reports were analyzed. There were 244 (79%) normal, 50 (16%) abnormal and 15 (5%) inconclusive FISH results. There were no false‐positive or false‐negative results, but there were nine (3%) clinically significant chromosomal abnormalities not detectable by FISH. Of the 50 women with abnormal FISH results, 26 (52%) elected to terminate the pregnancy prior to the availability of the standard chromosome analysis. In two of the fetuses with trisomy 21 no abnormalities were reported by ultrasound examination. Our experience indicates that interphase FISH results played an important role in decision making, especially for pregnancies close to 24 weeks' gestation. Standard karyotype analysis is still required for detection of chromosome abnormalities not detectable by interphase FISH techniques and for clarification of unusual or inconclusive FISH results. Copyright © 2001 John Wiley & Sons, Ltd.
Confined placental mosaicism for trisomy 14 and maternal uniparental disomy in association with elevated second trimester maternal serum human chorionic gonadotrophin and third trimester fetal growth restriction
Authors: Towner Dena R. , Shaffer Lisa G. , Yang Sam P. , Walgenbach Donna D.
Published: August 2002

A case of confined placental mosaicism (CPM) and maternal uniparental isodisomy 14 identified after placental karyotype revealed trisomy 14 in a newborn with intrauterine growth restriction (IUGR) and minor dysmorphic features is reported. During the second trimester of the pregnancy, multiple marker screening revealed an increased risk for Down syndrome of >1 in 10. The maternal serum human chorionic gonadotrophin (MShCG) was markedly elevated at 4.19 MoM. Amniocentesis revealed a normal 46,XX karyotype. Fetal growth restriction has been associated with elevated MShCG and placental aneuploidy with CPM for chromosomes 2, 7, 9 and 16. The present case of CPM for chromosome 14 was also associated with fetal growth restriction and elevated second trimester MShCG, suggesting a common link. Further studies need to be done to determine if indeed elevation of second trimester MShCG is associated with increased risk of CPM. The present case again demonstrates the need to perform placental karyotype in unexplained fetal growth restriction. Copyright © 2001 John Wiley & Sons, Ltd.
A phenomenological study of chronic sorrow in people with type 1 diabetes
Authors: Hayes Mary
Published: August 2002

This qualitative study has been designed to examine chronic sorrow in a population of individuals with type 1 diabetes. Teel1defines chronic sorrow as ‘a recurring sadness interwoven with periods of neutrality; satisfaction and happiness’. The sample chosen are five adult subjects with type 1 diabetes for an average of 22.4 years. Data was collected using audio taped, semi‐structured, interviews. Tapes were transcribed and analysed. Four themes emerged; fear of the future, negative attitudes of others, regrets and difficulties in managing the condition. The study discusses the causes of sadness. Results are of relevance to people with diabetes, and those who care for them. Copyright © 2001 John Wiley & Sons, Ltd.
Outcome of insulin treatment in type 2 diabetic patients with secondary oral hypoglycaemic failure
Authors: Akber M. , Clegg C. , Connor S. , Casson I.F.
Published: August 2002

A retrospective survey was carried out in patients with type 2 diabetes who had secondary failure with oral hypoglycaemic agents. Data were collected from the case notes of 100 patients converted to insulin treatment attending the Diabetes Centre at Broadgreen Hospital. Ten patients died within the first year of conversion to insulin; four patients were lost to follow‐up. Outcomes were assessed in 86 patients, who completed at least 1 year on insulin after conversion, at 6 months and 12 months. 20 of these patients were studied at 24 months. There were 39 males and 47 females, aged from 34 to 87 years (mean 67 years). The duration of diabetes was from 6 months to 40 years (mean 11 years). At 6 months their mean HbA1c improved from 10.8 to 8.3%, and at 12 months it was 8.0% (p<0.01). BMI increased from (mean) 24.3 to 26.9 at 6 months and 27.3 at 12 months (p<0.01). 64% of the patients gained weight, and in 27% BMI increased to more than 30.

This effect persisted at 24 months in 20 patients. Where HbA1c improved from (mean) 10.5% at 0 months to 8.1% at 24 months (p<0.01), the BMI increased from 25.1 (mean) to 28.6 (mean) (p<0.01).

95% of patients felt better on insulin, even though most of these patients were reluctant to start insulin at first. One patient asked to stop insulin on social grounds. 20% patients experienced mild hypoglycaemia; only 3% had severe hypoglycaemia. The final total daily insulin dose varied between 14 and 112 units (mean 40 units), and could not be predicted. Insulin treatment is well tolerated, achieves better metabolic control and gives a feeling of well‐being but results in weight gain. Copyright © 2001 John Wiley & Sons, Ltd.
Quality assurance in diabetes care: a population‐based study
Authors: Lundman Berit , Engström Lars , Kallioinen Marcus
Published: August 2002

Study objective.

The aim was to evaluate to what degree the recommendations in a health care programme for diabetes were fulfilled.

Design.

A population based study. Information was obtained from medical records.

Settings.

One county with 125 000 inhabitants in Northen Sweden.

Patients: 4057 adult patients with either type 2 diabetes (n=3581) or type 1 diabetes (n=446).

Main results.

Of the patients 34% had good, 22% acceptable and 24% poor metabolic control. Documentation of HbA1c was missing for 22% of the patients. Of patients with type 2 95% were examined for nephropathy, 57% for retinopathy, 63% for neuropathy and 68% for peripheral circulation. The corresponding figures for patients with type 1 were 99%, 90%, 95% and 95% respectively.

Conclusions.

For patients with type 1 the aims of the health care programme were largely fulfilled concerning examination of long‐term complications. In this respect screening of patients with type 2 was unsatisfactory. There is a need to optimise both metabolic control and screening for long‐term complications for a large proportion of the patients. Copyright © 2001 John Wiley & Sons, Ltd.
CODE‐2† UK: our contribution to a European study of the costs of type 2 diabetes
Authors: Williams R. , Baxter H. , Bottomley J. , Bibby J. , Burns E. , Harvey J. , Sheaves R. , Young R.
Published: August 2002

CODE‐2 UK is the UK contribution to the Cost of Diabetes in Europe – Type 2 (CODE‐2) study, the first to examine the health care resource use of people with type 2 diabetes in more than one European country. CODE‐2 UK studied samples of people with type 2 diabetes from population based registers in Bradford, Jersey and Salford. Data on NHS resource use were obtained retrospectively, covering the period 1 January 1998 to 31 December 1998, from the registers and from primary and secondary care records. Hospital admissions and ambulatory care accounted for 36.2% and 37.7% of total direct costs, which were, on average, £1505 per patient per year. Oral anti‐diabetic drugs accounted for 2.7% of total costs. Based on these data and an estimated prevalence of type 2 diabetes in the UK of 2%, the estimated total annual NHS cost of type 2 diabetes is £1.8 billion or 4.1% of total NHS expenditure. Similar findings were evident in other European countries. Copyright © 2001 John Wiley & Sons, Ltd.
A retrospective case–control study of initiating insulin therapy in type 2 diabetes
Authors: Dickinson PJ , Dornhorst A , Frost GS
Published: August 2002

Objective.

To assess the impact of the introduction of insulin therapy in individuals with type 2 diabetes mellitus (DM) on weight gain, glycaemic control and serum lipids.

Design and subjects.

A retrospective study of weight gain and metabolic parameters among type 2 DM subjects initiated on insulin between 1993 and 1999 while attending the Hammersmith Hospital diabetic outpatient clinic in London, UK. A comparison of weight gain and access to dietetic advice, as assessed from the hospital records, was made on 148 type 2 DM outpatients (78 female, 53%) started on insulin and a control group of 53 type 2 diabetic subjects (26 female, 49%), with similar starting weights but not taking insulin.

Results.

The insulin treated subjects compared with the non‐insulin treated controls were of similar age and disease duration. The time from diagnosis to initiation of insulin was 6 ± 4.76 years (SD). The year prior to insulin initiation (year −1) was considered the reference year when the weights of the two groups were similar but the HbA1c values higher in the group that went on to insulin than the controls (10.5 ± 2.1% versus 7.6 ± 2.2%, p < 0.001). After the first year of insulin treatment the HbA1c fell by 1.5 ± 2.1% (p < 0.001) and the fasting blood glucose (FBG) by 4 ± 5.8 mmol/L (p < 0.001). No change in HBA1c or FBG occurred during this time in the control subjects. There were no changes in plasma lipids, cholesterol or triglyceride, nor was there any change in blood pressure during this study in either group. Despite an improvement in glycaemic control in the insulin treated group, their HbA1c and FBGs remained higher than those of the control (8.5 versus 7.3%, p < 0.001, and 10.3 versus 9.1 mmol/L, p < 0.001 respectively). Weight gain after one year of insulin treatment was 4.2 ± 4.0 kg, equivalent to 6% increase in body weight. This retrospective study showed that only 26% of subjects started on insulin saw a dietitian prior to insulin treatment, even though over 20% had patients had a BMI greater than 30 kg/m2.

Conclusion.

Glycaemic control but not fasting lipids improved significantly following a year of insulin treatment; however, this was associated with an average weight gain of 6%. During this time 74% of subjects in whom insulin treatment was started had no access to a dietitian. Prospective studies are required to determine whether increased access to specialist dietetic programmes in patients starting insulin therapy can limit weight gain. Copyright © 2002 John Wiley & Sons, Ltd.
Prospective cohort study of adverse events monitored by hospital pharmacists
Authors: Emerson Angela , Martin Richard M. , Tomlin Mark , Mann Ronald D.
Published: August 2002

Purpose

To examine the feasibility of pharmacist‐led intensive hospital monitoring of adverse events (AEs) associated with newly marketed drugs.

Subjects/setting

303 patients admitted to Southampton Hospitals who were prescribed selected newly marketed drugs during their inpatient stay in 1998.

Methods

Prospective observational study. Patients were identified from computerized pharmacy records, clinical pharmacist ward rounds, dispensary records or via nursing staff. The pharmacist reviewed medical notes and recorded AEs, suspected adverse drug reactions (ADRs) and reasons for stopping drugs.

Outcomes

Incidence of AEs, ADRs; proportionate agreement between the physician's and pharmacist's event recording.

Results

303 patients were monitored. Of the patients taking newly marketed drugs 92% were identifiable using pharmacy computer systems and pharmacist ward visits. There were 21 (7%) suspected ADRs detected during this pilot study. The types of adverse events detected were broadly similar to those identified by general practice‐based prescription event monitoring. However, biochemical changes featured more frequently than in general practice. Differences between adverse events recorded by pharmacist and physician were systematic and attributed to differences in event coding.

Conclusion

Pharmacist‐led monitoring in a typical NHS hospital setting was effective at detecting ADRs in newly marketed drugs. However, this effort might have been substantially less time‐consuming and more effective were electronic patient records (EPRs) available. Pharmacy computer systems are not designed to be patient focused and are therefore unable to identify patients taking newly marketed drugs. It is argued that future EPR and computerised patient‐specific prescribing systems should be designed to capture this data in the same way as some US systems are currently able to do. Copyright © 2001 John Wiley & Sons, Ltd.
An audit of the use of antirheumatic drugs in a North Indian referral hospital
Authors: Balakrishnan S. , Bambery Pradeep , Gupta Nidhi , Pandhi Promila
Published: August 2002

Objective

This study was conducted with the aim of auditing the pattern of use of antirheumatic drugs in a tertiary care hospital in Northern India.

Methods

The study was carried out in 1000 patients recruited sequentially from the clinic for a period of 1 year (January to December 1999). Patient data such as age, sex, income, family size, diagnosis, duration of illness, drugs prescribed/duration, adverse drug reaction were noted and used to calculate core drug use indicators and pattern of drug use.

Results

The pattern of drug use was in accordance with the standard practices followed internationally. In rheumatoid arthritis the most common prescriptions were for non‐steroidal antiinflammatory drugs (NSAIDs) alone, followed by the combination of NSAIDs, disease modifying agents (DMARDs) and steroids. Of the NSAIDs diclofenac was the most frequently prescribed drug, while chloroquine was the most commonly used DMARD. The most commonly seen adverse drug reactions were gastritis, Cushings syndrome and decreased visual acuity.

Conclusions

In conclusion, this study has demonstrated that in this clinic, the pattern of use of antirheumatic drugs follows standard guidelines. Copyright © 2001 John Wiley & Sons, Ltd.
Risk factors for the development of Clostridium difficile toxin‐associated diarrhoea: a pilot study
Authors: Aziz E. E. , Ayis S. , Gould F. K. , Rawlins M. D.
Published: August 2002

This study was a pilot investigation of risk factors for the development of Clostridium difficile toxin‐associated diarrhoea and in particular the differential influence of antimicrobial agents. The study was a retrospective case—control design conducted at Freeman Hospital, Newcastle upon Tyne. Cases were inpatients with stool positive C. difficile toxin diarrhoea and two controls were drawn for each case matched for age (+/−5 years) and type of admission (emergency or elective). Using conditional logistic regression analysis, cephalosporins and erythromycin were found to be statistically significantly associated with Clostridium difficile toxin associated‐diarrhoea. The results form the basis for designing a larger, prospective study. Copyright © 2001 John Wiley & Sons, Ltd.
Antidepressant medication and suicide in Sweden
Authors: Carlsten Anders , Waern Margda , Ekedahl Anders , Ranstam Jonas
Published: August 2002

Objective

To explore a possible temporal association between changes in antidepressant sales and suicide rates in different age groups.

Methods

A time series analysis using a two‐slope model to compare suicide rates in Sweden before and after introduction of the selective serotonin reuptake inhibitors, SSRIs.

Results

Antidepressant sales increased between 1977–1979 and 1995–1997 in men from 4.2 defined daily doses per 1000 inhabitants and day (DDD/t.i.d) to 21.8 and in women from 8.8 to 42.4. Antidepressant sales were twice as high in the elderly as in the 25–44‐year‐olds and eight times that in the 15–24‐year‐olds. During the same time period suicide rates decreased in men from 48.2 to 33.3 per 105 inhabitants/year and in women from 20.3 to 13.4. There was significant change in the slope in suicide rates after the introduction of the SSRI, for both men and women, which corresponds to approximately 348 fewer suicides during 1990–1997. Half of these ‘saved lives’ occurred among young adults.

Conclusion

We demonstrate a statistically significant change in slope in suicide rates in men and women that coincided with the introduction of the SSRI antidepressants in Sweden. This change preceded the exponential increase in antidepressant sales. Copyright © 2001 John Wiley & Sons, Ltd.
Privacy considerations in the context of an Australian observational database
Authors: Duszynski Katherine M. , Beilby Justin J. , Marley John E. , Walker Don C. , Pratt Nicole L.
Published: August 2002

Observational databases are increasingly acknowledged for their value in clinical investigation. Australian general practice in particular presents an exciting opportunity to examine treatment in a natural setting. The paper explores issues such as privacy and confidentiality—foremost considerations when conducting this form of pharmacoepidemiological research. Australian legislation is currently addressing these exact issues in order to establish clear directives regarding ethical concerns. The development of a pharmacoepidemiological database arising from the integration of computerized Australian general practice records is described in addition, to the challenges associated with creating a database which considers patient privacy. The database known as ‘Medic‐GP’, presently contains more than 950 000 clinical notes (including consultations, pathology, diagnostic imaging and adverse reactions) over a 5‐year time period and relates to 55 000 patients. The paper then details a retrospective study which utilized the database to examine the interaction between antibiotic prescribing and patient outcomes from a community perspective, following a policy intervention. This study illustrates the application of computerized general practice records in research. Copyright © 2001 John Wiley & Sons, Ltd.
Ethical issues in a Brazilian hospital
Authors: de Castro Mauro Silveira , Goldim José Roberto , Ferreira Maria Beatriz Cardoso
Published: August 2002

Purpose

The objective of this paper is to discuss ethical issues such as data protection, confidentiality, and patient freedom taking two ongoing studies as examples.

Methods

The two studies are being carried out at a public hospital in southern Brazil. Study 1 evaluates inadequate use of drugs (mainly vancomycin) and aims at reviewing criteria for drug use control. It includes records of 100 patients whose prescriptions are dispensed at the hospital's pharmacy. A major ethical concern in this study was to ensure data confidentiality. Study 2 evaluates treatment adherence by hypertension patients with a focus on hydrochlorothiazide. Here, in addition to data protection, a major ethical concern was the ability of patients to understand the informed consent form and therefore freely enter or refuse to enter the study. Both projects were approved by the Institutional Review Board at Hospital de Clínicas de Porto Alegre.

Results

In both studies, data confidentiality is ensured by the removal of all personal information from the forms used for data analysis. In Study 2, readability of the informed consent was considered adequate by the IRB for the population served by the clinic, and one‐third of the patients who were contacted agreed to participate in the study.

Conclusions

To obtain reliable results, basic ethical principles must be observed throughout the planning and execution of research projects, whether data are obtained from medical records or from actual interaction with patients. Thus, monitoring by an Institutional Review Board or equivalent is of paramount importance. Copyright © 2001 John Wiley & Sons, Ltd.
Ethical challenges in pharmacoepidemiological research in Colombia
Authors: Dennis Rodolfo J. , Lozano Juan M.
Published: August 2002

Purpose

To illustrate and to discuss some ethical challenges encountered during pharmacoepidemiological research in a developing country (Colombia), as well as the decisions made to solve them.

Methods

The authors in Bogotá describe three recent studies. The first one collected data from clinical records to evaluate the prescriptions patterns in recently graduated physicians. The second used an interrupted time series design, with a set of observations prior and after a combined intervention, to assess whether it improved the quality of intravenous antibiotic prescribing practices in a university‐based hospital. The third evaluated pharmacists' advice in childhood acute respiratory infection and acute diarrhea through a community survey, followed by focus groups and in‐depth interviews of key informers.

Results

The ethical issues raised by these studies include the need for obtaining informed consent from participants (physicians in Study 1 and drug sellers in Study 3), deciding when to intervene in case of gross prescription mistakes detected during the collection of data as part of the time series assessment (Study 2), the use of simulated clients to collect data in the community survey, and the use of study resources to buy, in some cases, useless medications (Study 3).

Conclusion

Although ethical challenges in pharmacoepidemiology in non‐industrialized countries like Colombia may be different from those in developed nations, ethical principles that guide research remain the same. The processes to safeguard these principles in Colombia for virtually all research are also universal in nature, and include the ethical review committee, subject privacy, informed consent, and disclosure of funding sources. Copyright © 2001 John Wiley & Sons, Ltd.
Pharmacoepidemiology—an Irish perspective
Authors: Williams D. , Feely J.
Published: August 2002

The Irish healthcare system is a mixture of free, state‐supported and private medicine. The state‐supported General Medical Services (GMS) scheme maintains a large prescription database, which has been used to conduct pharmacoepidemiological studies in Ireland. The dataset is anonomysed thus maintaining patient and prescriber confidentiality. Three recent studies using this data are described, two of which outline the effect of regulatory advice and the media on prescribing patterns and one which describes the development of an index of prescribing quality which may be applied to prescription data. The GMS prescription database is presently being complemented by a database for some 0.7 million people who seek re‐imbursement for prescriptions from individuals or families in excess of £42 per month which together will have an important role for the continued development of pharmacoepidemiology in Ireland. Copyright © 2001 John Wiley & Sons, Ltd.
Ethical issues related to retrospective drug utilization studies in South Africa
Authors: Truter Ilse
Published: August 2002

Purpose

The purpose of the manuscript is to discuss the ethical issues related to pharmacoepidemiological research in South Africa, with specific emphasis on three recently performed retrospective drug utilization studies.

Methods

Ethical considerations relating to three retrospective drug utilization studies on hyperlipidaemia, diabetes and tricyclic antidepressants are discussed.

Results

Computerized medication records were obtained from three different organizations after formal proposals had been submitted. The information contained in the data sets varied, and in some instances, a fair amount of manual coding had to be performed to make the data useable for research purposes. The research was not sponsored by the private pharmaceutical sector and this minimized the potential for any bias in the studies. Data privacy and confidentiality were maintained at all times. No patient could be traced, and it was also not possible to determine which medical practitioners were involved in the prescribing of the drugs.

Conclusions

Retrospective drug utilization studies are a relatively easy, inexpensive and uncomplicated method to comment on the prescribing of drugs in large patient populations provided that ethical principles related to confidentiality and data privacy are adhered to. Copyright © 2001 John Wiley & Sons, Ltd.
How do pharmaceutical companies handle consumer adverse drug reaction reports? An overview based on a survey of French drug safety managers and officers
Authors: Fleuranceau‐Morel P.
Published: August 2002

It is surprising to see how consumer Adverse Drug Reaction (ADR) reports have been continuously increasing for the last few years in Europe. This probably results from the influence of United States (US) market where the patients feels justified in telephoning the pharmaceutical companies directly with queries regarding their treatment. The growing number of alternative sources of information (e.g. health and popular magazines, spots on radio and TV etc.) to which a consumer is exposed has added to this growth too. The changing relationship between patients and doctors may also contribute to this phenomenon. It is then interesting to evaluate the way pharmaceutical companies currently deal with consumer ADR reports. The management of consumer ADR reporting was investigated by means of a questionnaire sent to 46 French drug safety managers and drug safety officers (DSOs) of multinational pharmaceutical companies. The analysis of the survey stressed the fact that pharmaceutical companies should be prepared to face up to an increase in the number of consumer ADR reports. It clearly appears that the consumers who telephone to register side‐effects should be forwarded to a trained DSO with medical or pharmaceutical background and the communication skills acquired through specific training. This person should also be able to release adequate product information validated by his/her own company. The influence of the US market seems to be changing the way pharmaceutical companies deal with consumer ADR reports. Nowadays, these reports are entered into a drug safety database by most of the companies without previously having contacted the patient's general practitioner (GP) or specialist for medical confirmation. Lastly, the drug safety managers and DSOs consulted have divided opinions about the usefulness of call centres and e‐mails as tools for ADR reporting. But both tools are globally rejected by the pharmaceutical companies as a reliable means of reporting. As stated in this article, the reporting of ADRs via e‐mail would cause real problems for the drug safety units. Finally, they consider that telephone call centres should be restricted to a specific communication problem such as crisis management or Dear Dr letters. Copyright © 2002 John Wiley & Sons, Ltd.
Risk of irritable bowel syndrome among asthma patients
Authors: Huerta Consuelo , Rodríguez Luis Alberto García , Wallander Mary‐Ann , Johansson Saga
Published: August 2002

Background

An association between Irritable Bowel Syndrome (IBS) and bronchial hyper‐responsiveness has been suggested. Only a few studies have specifically studied the association between IBS and asthma.

Aim

To estimate the incidence rate of IBS among asthma patients and to compare it with the general population. We also examined the association between use of asthma drugs, specifically corticosteroids, and IBS.

Methods

Population‐based cohort study using the General Practice Research Database (GPRD) in the UK. The cohort comprised a random sample of 50 000 asthma patients aged 10–79 years and a similar number of sex‐and age‐matched individuals free of asthma and identified from the source population. A nested case–control analysis was performed within the asthma cohort to examine the association between asthma drugs and IBS.

Results

The incidence rate of IBS in the asthma cohort was 2.5 per 1000 persons‐years and 2.0 in the general population. The relative risk (RR) was 1.3 (95% CI 1.1–1.5). A medical history of neurotic and psychologic disorders, pain‐related diseases and gastroenteritis were all associated with the occurrence of IBS. In the asthma cohort, current users of oral steroids presented a RR of 0.5 (95% CI 0.2–1.2) for developing IBS. The risk estimate was similar in short‐and long‐term users of steroids.

Conclusions

We found a slightly increased risk of IBS in asthma patients compared to the general population and that the risk of IBS was reduced by use of oral steroids in asthma patients. Additional studies in the general population are necessary in order to confirm whether use of corticosteroids irrespective of asthma has a protective effect on the risk of IBS. Copyright © 2001 John Wiley & Sons, Ltd.
Automated support for pharmacovigilance: a proposed system
Authors: Bright Roselie A. , Nelson Robert C.
Published: August 2002

Governments, manufacturers, and other entities are interested in adverse event surveillance of marketed medical products. FDA's Center for Drug Evaluation and Research redesigned the post‐marketing adverse reaction surveillance process to use the advantages of new technology. As part of this effort, a ‘Pharmacovigilance Working Group’ designed a new strategy for the review and analyses of adverse event reports received by FDA. It created requirements which divided signal detection into five tiers: (1) Single ‘urgent’ reports would be sent to reviewers' workstations nightly for immediate attention. Reviewers would be able to customize definitions of ‘urgent’ (events that should not wait for aggregate review). (2) Single urgent reports would be placed in a context matrix containing historical counts of similar events to aid in initial interpretation. (3) In this first level of aggregate review, graphical displays would highlight patterns within all the reports, both urgent and non‐urgent, and (4) periodic drug‐specific tabled‐based reports would display the newly received reports across a pre‐defined variety of displays. These four tiers would produce passive and criteria‐based results which would be presented to safety reviewers' electronic workstations. (5) Active query capabilities (routine, such as age, sex, and year distributions, as well as ad hoc) would be available for exploring alerted issues. The historical database would be migrated into the new format. All historical and new reaction data would be coded with the new MedDRA (Medical Dictionary for Regulatory Activities) scheme. The strategy was to design a full data capture system which effectively exploits current computing advances and technical performance to automate many aspects of initial adverse event review, supporting more efficient and effective clinical assessment of safety signals. Published in 2002 by John Wiley & Sons, Ltd.
Hyponatremia and syndrome of inappropriate anti‐diuretic hormone reported with the use of Vincristine®: an over‐representation of Asians?
Authors: Hammond Isaac W. , Ferguson Jeffrey A. , Kwong Kenneth , Muniz Edmundo , Delisle Frank
Published: August 2002

Purpose

This retrospective study used a pharmaceutical company's global safety database to determine the reporting rate of hyponatremia and/or syndrome of inappropriate secretion of anti‐diuretic hormone (SIADH) among vincristine‐treated patients and to explore the possibility of at‐risk population subgroups.

Method

We searched the Eli Lilly and Company's computerized adverse event database for all reported cases of hyponatremia and/or SIADH as of 1 November 1999 that had been reported during the use of vincristine.

Results

A total of 76 cases of hyponatremia and/or SIADH associated with vincristine use were identified. The overall reporting rate was estimated to be 1.3/100 000 treated patients. The average age of patients was 35.6 ± 28.3 years, and 62% were males. Approximately 75% of the patients were receiving treatment for leukemia or lymphoma. Among the 39 reports that included information on race, the racial distribution was: 1 Black, 3 Caucasian, and 35 Asian.

Conclusion

Our data suggest that Asian patients may be at increased risk of hyponatremia and/or SIADH associated with vincristine use. Although the overall reported rate of SIADH associated with vincristine is very low, physicians caring for Asian oncology patients should be aware of this potential serious but reversible adverse event. Copyright © 2002 John Wiley & Sons, Ltd.
Part 1. Qualitative comparison between polymer and monomer model compound sulfonation
Authors: Daoust D , Devaux J , Godard P
Published: August 2002

The sulfonation kinetics of fluorine ended poly(ether ether ketone) (PEEK) in solution in 95.9% and 96.8% concentrated sulfuric acid was studied with the help of a model compound representative of the PEEK chain repeat unit. The reaction rate of the model compound sulfonation was found to be first order with respect to the aromatic ring to be sulfonated. Consequently, PEEK kinetic data were treated following a first order with respect to the unsulfonated repeat unit concentration. Two rate‐slowing effects were detected. They were attributed to ‘long range’ electronic effects resulting from the inductive nature of the fluorine atom, and from the electron‐withdrawing character of the grafted sulfonic acid group.

© 2001 Society of Chemical Industry