bluuebunny/crossref_metadata_2025 huggingface dataset:
Summary Australian and New Zealand Clinical Practice Guideline for the Management of Anorexia Nervosa(2003)
Authors: Beumont Pierre , Hay Phillipa , Beumont Rochelle ,   RANZCP Multidisciplinary Clinical Practice Guideline Team for the Treatment of Anorexia Nervosa
Published: May 2003

Objective: To provide a summary of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) Clinical Practice Guideline for the Management of Anorexia Nervosa (AN).

Conclusions: Anorexia nervosa affects only a small proportion of the Australian and New Zealand population but it is important because it is a serious and potentially life-threatening illness. Sufferers often struggle with AN for many years, if not for life, and the damage done to their minds and bodies may be irreversible. Anorexia nervosa is characterized by a deliberate loss of weight and refusal to eat. Overactivity is common. Approximately 50% of patients also use unhealthy purging and vomiting behaviours to lose weight. There are two main areas of physical interest: the undernutrition and mal-nutrition of the illness and the various detrimental weight-losing behaviours themselves. Basic psychopathology ranges from an over-valued idea of high salience concerning body shape through to total preoccupation and eventually to firmly held ideas that resemble delusions. Comorbid features are frequent, especially depression and obsessionality. It is inadvisable in clinical practice to apply too strict a definition of AN because to do so excludes patients in the early stage of the illness in whom prompt intervention is most likely to be effective. The best treatment appears to be multidimensional/multidisciplinary care, using a range of settings as required. Obviously, the medical manifestations of the illness need to be addressed and any physical harm halted and reversed. It is difficult to draw conclusions about the efficacy of further treatments. There is a paucity of clinical trials, and their quality is poor. Furthermore, the stimuli for developing AN are varied, and the psychotherapy options to address these problems need to be tailored to suit the individual patient. Because there is no known ‘chemical imbalance’ that causes the illness, no one drug offers relief. There is a high rate of relapse, and some patients are unable to recover fully. Because AN is a psychiatric illness, a psychiatrist should always be involved in its treatment. All psychiatrists should be capable of assuming this responsibility. Because cognitive behavioural methods are generally accepted as the best mode of therapy, a clinical psychologist should also be involved in treatment. Because medical manifestations are important, someone competent in general medicine should always be consulted. The optimal approach is multidisciplinary or at least multiskilled, with important contributions from psychologists, general practitioners, psychiatric nurses, paediatricians, dietitians and social workers.
Consumer and Carer Participation in Mental Health Services
Authors: Lloyd Chris , King Robert
Published: May 2003

Objective: To clarify the meaning of consumer and carer participation in mental health services, to identify reasons why consumer participation is important both to consumers and to services, and to discuss barriers to participation and ways of overcoming these barriers.

Conclusions: Consumer and carer participation has been promoted as part of the National Mental Health Strategy and has the potential to empower consumers and their carers and to improve mental health services. Barriers to consumer participation include professional staff attitudes and resource allocation. Guidelines are provided to assist services to address these barriers and increase the level of consumer and carer participation in both clinical decision-making and service development.
Abolishing Waiting Lists in an Aged Psychiatry Service
Authors: George Kuruvilla
Published: May 2003

Objective: Waiting lists are a problem for most aged psychiatry services. The present paper describes how an aged psychiatry service managed to abolish the waiting list for admission to their acute inpatient unit.

Method: The process of developing and implementing a new set of principles and practice for the unit is described.

Results: There was a clear and almost immediate difference noted in that the number of admissions and discharges increased and the length of stay and occupancy rates decreased.

Conclusions: It is possible to abolish waiting lists without increasing the bed numbers in an aged psychiatry service.
Summary Australian and New Zealand Clinical Practice Guideline for the Management of Adult Deliberate Self-Harm (2003)
Authors: Boyce Philip , Carter Greg , Penrose-Wall Jonine , Wilhelm Kay , Goldney Robert
Published: May 2003

Objective: To provide a summary of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) Clinical Practice Guideline for the Management of Deliberate Self-Harm.

Conclusions: This guideline covers self-harm regardless of intent. It is an evidence-based guideline developed from a systematic review of epidemiological, treatment and medico-legal literature. All patients presenting to hospital after deliberate self-harm should be comprehensively assessed to detect and treat the high rates of mental disorders, alcohol and other drug problems and personality disorders in this group. General hospital management aims to ensure safety from further self-harm, assess and treat injuries; prevent disablement and death as a result of injuries or poisoning and manage suicide risk by ensuring prompt psychiatric referral and mobilizing social supports. Psychological management aims to detect and treat underlying mental disorders, reduce distress and enhance coping skills and thereby, reduce repeat episodes and habituation of self-harm. Managing suicide risk is a continuous responsibility and suicide vulnerability may persist long-term in some patients. There is little firm guidance from the literature on treatment efficacy to guide ongoing psychiatric management. Studies are often compromised because between 41 and 70% of patients do not attend follow up. The mainstay of psychological care remains the treatment of underlying Axis I and Axis II disorders. Cognitive-behavioural therapy (CBT) and problem-orientated approaches appear promising for reducing repeated self-harm for most patient groups but no single treatment has confirmed superiority. Dialectical behaviour therapy (DBT) appears to confer most benefit. Self-harm may follow some forms of in-depth therapy in some vulnerable individuals. There is no one recommended pharmacological treatment specifically to reduce self-harming behaviours. Lithium may have antiself-harm properties for some groups with bipolar disorder. There is emerging evidence for selfharm reduction using clozapine for patients with schizophrenia and schizoaffective disorder.
Improving the Safety of Mental Health Services
Authors: Tobin Margaret , Wilson Andrew , Graham Rebecca , Richardson Madeline
Published: May 2003

Objective: To examine national and international initiatives for the provision of safer health care and their applicability to mental health services.

Conclusions: There is a need for an integrated, uniform approach to the development and implementation of safety standards in mental health services. A partnership approach involving key stakeholders and the consideration of an initial set of safety indicators requires consideration.
Scope for Psychosocial Treatments in Psychosis: An Overview of Collaborative Therapy
Authors: Gilbert Monica , Miller Kathryn , Berk Lesley , Ho Velma , Castle David
Published: May 2003

Objectives: The psychosocial needs of people with psychotic disorders are not being addressed adequately. The present paper outlines a proposed framework that will help to meet some of this deficit and deliver psychosocial treatments for these individuals, as part of routine clinical practice.

Conclusions: The recent Australian study on low prevalence (psychotic) disorders found that, although most Australians (91%) with a psychotic illness were taking medication, few were receiving adequate psychosocial support from mental health services; fully 47% of these saw the need for a particular type of service that was not able to be accessed by them, either because of it simply not being available or not being affordable. The programme described herein will develop, evaluate and disseminate comprehensive modular treatment packages addressing the psychosocial needs of people with psychotic disorders. It is novel in terms of the comprehensiveness of the approach, the rigour of the evaluation (using a controlled experimental design), and the extent of intersectoral and multidisciplinary involvement in mapping needs, developing the interventions, and dissemination. The potential impact for mental health consumers with psychosis is enormous because currently there is no coherent and consistent approach to addressing their psychosocial needs. The impact for the scientific community will be great because there is currently very little by way of controlled trial data in this important area of activity.
Origins of Early Intervention in First-Episode Psychosis
Authors: Sanbrook Mark , Harris Anthony
Published: May 2003

Objective: To outline reasons contributing to the delayed introduction of early intervention strategies for first-episode psychosis, followed by a discussion of recent factors that have supported the increased use of these strategies.

Conclusions: The reasons for this delay include pessimistic beliefs carried over from early in the 20th century about the prognosis of schizophrenia, the central role of the institution in psychiatric history, and the need for a working neurobiological model for psychosis. The discovery of the antipsychotic drugs, the process of deinstitutionalization, and new conceptualizations of schizophrenia have been necessary precursors to current best practice treatments. In recent years these factors have been complemented by the increasing influence of consumer and family advocacy groups, and government policy initiatives.
The selection of triple therapy for Helicobacter pylori eradication in chronic renal insufficiency
Authors: Sheu B.‐S. , Huang J.‐J. , Yang H.‐B. , Huang A.‐H. , Wu J.‐J.
Published: May 2003

Aim: To establish a triple therapy regimen for Helicobacter pylori eradication in patients with chronic renal insufficiency.

Methods: Eighty‐eight patients with chronic renal insufficiency and H. pylori infection were evenly randomized into two groups receiving 1‐week lansoprazole, 30 mg, clarithromycin, 500 mg, and either amoxicillin, 750 mg, or metronidazole, 500 mg, twice daily. The adverse events and compliance with triple therapy were reviewed at the week 1 visit. Patients provided stool samples at week 6 to assess the success of H. pylori eradication by H. pylori‐specific stool antigen. The serum creatinine levels were monitored at enrolment, at weeks 1, 2 and 6 and on any unscheduled visit after triple therapy.

Results: The success of H. pylori eradication was higher in the lansoprazole–clarithromycin–metronidazole group than in the lansoprazole–clarithromycin–amoxicillin group (intention‐to‐treat analysis: 84% vs. 66%, P < 0.05: per protocol analysis: 93% vs. 76%, P < 0.05). Complete drug compliance was also better in the lansoprazole–clarithromycin–metronidazole group than in the lansoprazole–clarithromycin–amoxicillin group (77% vs. 52%, P < 0.05). Patients in the lansoprazole–clarithromycin–metronidazole group had a lower risk of acute renal failure than those in the lansoprazole–clarithromycin–amoxicillin group (2% vs. 18%, P < 0.05; relative risk, 0.128, 95% confidence interval, 0.016–0.979).

Conclusions: Triple therapy with metronidazole and clarithromycin, but not amoxicillin, can be used for H. pylori eradication in patients with chronic renal insufficiency, because it is more effective, well tolerated and less likely to cause deterioration of renal function.
Rescue therapy with tacrolimus is effective in patients with severe and refractory inflammatory bowel disease
Authors: Baumgart D. C. , Wiedenmann B. , Dignass A. U.
Published: May 2003

Background : Oral tacrolimus, approved for the prophylaxis of organ rejection in liver or kidney transplants, has been reported to be effective in anecdotal cases of refractory inflammatory bowel disease.

Aim : To evaluate the usefulness of low‐dose oral tacrolimus in refractory inflammatory bowel disease.

Methods:  Thirty‐one adult Caucasian patients with steroid‐dependent (n = 15) or steroid‐refractory (n = 16) inflammatory bowel disease (Crohn's disease, n = 6; ulcerative colitis, n = 23; pouchitis, n = 2) were enrolled. Tacrolimus (0.1 mg/kg body weight per day) was administered orally in 30 patients and initially intravenously in one patient (0.01 mg/kg body weight per day), aiming for serum trough levels of 4–6 ng/mL. The median treatment duration was 12 months (range, 1–137 months).

Results : Twenty‐eight patients (90.3%) experienced a clinical and laboratory response and 20 (64.5%) went into remission. One ulcerative colitis patient and two Crohn's disease patients did not improve. Three ulcerative colitis patients (9.7%) were colectomized at 1, 12 and 24 months after tacrolimus initiation. In 19 of 23 patients (82.6%) taking steroids, steroids were reduced or discontinued. Side‐effects included a temporary rise of creatinine (n = 3, 9.7%), tremor or paraesthesias (n = 3, 9.7%), hyperkalaemia (n = 1, 3.2%), hypertension (n = 1, 3.2%) and an opportunistic infection (n = 1, 3.2%).

Conclusion : Oral tacrolimus is safe and effective in refractory inflammatory bowel disease.
Infliximab in refractory pouchitis complicated by fistulae following ileo‐anal pouch for ulcerative colitis
Authors: Viscido A. , Habib F. I. , Kohn A. , Papi C. , Marcheggiano A. , Pimpo M. T. , Vernia P. , Cadau G. , Caprilli R.
Published: May 2003

Aim:  To determine the efficacy of infliximab in the treatment of chronic refractory pouchitis complicated by fistulae following ileal pouch‐anal anastomosis for ulcerative colitis.

Methods:  This open study included seven patients (four females, three males) with chronic refractory pouchitis complicated by fistulae. Pouchitis was diagnosed by clinical, endoscopic and histological criteria. The sites of the fistulae were as follows: pouch‐bladder in one, vaginal in three, perianal in two, and both vaginal and perianal in one. Extra‐intestinal manifestations (erythema nodosum, arthralgia) were present in four patients. Crohn's disease was carefully excluded in all patients after re‐evaluation of the history, re‐examination of the original proctocolectomy specimen and examination of the proximal small bowel. All patients had been treated with antibiotics and three with steroids. Patients received infliximab, 5 mg/kg, at 0, 2 and 6 weeks. Azathioprine (2.5 mg/kg) was also started for all patients as bridge therapy. Clinical response was classified as complete, partial or no response. Fistulae closure was classified as complete (cessation of fistulae drainage and total closure of all fistulae), partial (a reduction in the number, size, drainage or discomfort associated with fistulae) or no closure. The pouchitis disease activity index and quality of life were also used as outcome measures.

Results:  Clinically, all patients improved. At the 10‐week follow‐up, six of the seven patients had a complete clinical response, and five had complete fistulae closure. At the 10‐week follow‐up, the median pouchitis disease activity index decreased from 12 (baseline) (range, 10–15) to 5 (range, 3–8); the median quality of life decreased from 37 points (range, 33–40) to 14 (range, 9–18). Erythema nodosum and arthralgia showed complete remission soon after the first infusion of infliximab.

Conclusions:  These preliminary results indicate that infliximab may be recommended for the treatment of refractory pouchitis complicated by fistulae following ileal pouch‐anal anastomosis for ulcerative colitis.
Meta‐analysis: comparing the efficacy of proton pump inhibitors in short‐term use
Authors: Klok R. M. , Postma M. J. , Van Hout B. A. , Brouwers J. R. B. J.
Published: May 2003

Background:  Proton pump inhibitors have a prominent role in the management of acid‐related diseases. Controlling expenses on proton pump inhibitors would yield great economic benefits for Dutch health care.

Aim:  To investigate whether clinical differences in proton pump inhibitors exist.

Methods:  We searched Medline, EMBASE and the Cochrane Library. We identified papers in English, German, French or Dutch in which two or more proton pump inhibitors were compared under the same clinical conditions in gastro‐oesophageal reflux disease, peptic ulcer disease or Helicobacter pylori eradication. The pooled relative risks were calculated using the Mantel–Haenszel method.

Results:  Two significant differences were found in the proton pump inhibitors compared. In gastro‐oesophageal reflux disease, esomeprazole 40 mg was superior to omeprazole 20 mg (relative risk, 1.18; 95% confidence interval, 1.14–1.23). In peptic ulcer disease, pantoprazole 40 mg was superior to omeprazole 20 mg (relative risk, 1.07; 95% confidence interval, 1.02–1.13). In Helicobacter pylori eradication, no significant differences were found.

Conclusions:  Both significant differences found were in favour of the highest dose of proton pump inhibitor on a milligram basis. This indicates that the difference may be dose dependent and not proton pump inhibitor specific. Therefore, when prescribing proton pump inhibitors, arguments other than clinical efficacy, such as those related to pharmaco‐economics, may be considered.
Refeeding syndrome: effective and safe treatment with Phosphates Polyfusor
Authors: Terlevich A. , Hearing S. D. , Woltersdorf W. W. , Smyth C. , Reid D. , Mccullagh E. , Day A. , Probert C. S. J.
Published: May 2003

Background:  Severe hypophosphataemia associated with refeeding syndrome requires treatment with intravenous phosphate to prevent potentially life‐threatening complications. However, evidence for replacement regimens is limited and current regimens are complex and replace phosphate inadequately.

Aim:  To assess the effectiveness and safety of 50 mmol intravenous phosphate infusion, given as a ‘Phosphates Polyfusor’, for the treatment of severe hypophosphataemia in refeeding syndrome.

Methods:  Patients with refeeding syndrome and normal renal function received a Phosphates Polyfusor infusion for the treatment of severe hypophosphataemia (< 0.50 mmol/L). The outcome measures were serial serum phosphate, creatinine and calcium concentrations for 4 days following phosphate infusion and adverse events.

Results:  Over 2 years, 30 patients were treated. Following treatment, 37% of cases had a normal serum phosphate concentration and 73% had a serum phosphate concentration of > 0.5 mmol/L within 24 h. Ten patients required more than one Phosphates Polyfusor infusion. Within 72 h, 93% of cases had achieved a serum phosphate concentration of ≥ 0.50 mmol/L. No patient developed renal failure. Three episodes of transient mild hyperphosphataemia were recorded. Four patients developed mild hypocalcaemia.

Conclusions:  This is the largest published series of the use of intravenous phosphate for the treatment of severe hypophosphataemia (< 0.50 mmol/L), and is the most effective regimen described. All patients had refeeding syndrome and were managed on general wards.
Systematic review: antacids, H2‐receptor antagonists, prokinetics, bismuth and sucralfate therapy for non‐ulcer dyspepsia
Authors: Moayyedi P. , Soo S. , Deeks J. , Forman D. , Harris A. , Innes M. , Delaney B.
Published: May 2003

Background: Evidence for the effectiveness of antacids, histamine‐2 receptor antagonists, bismuth salts, sucralfate and prokinetic therapy in non‐ulcer dyspepsia is conflicting.

Aim: To conduct a systematic review evaluating these therapies in non‐ulcer dyspepsia.

Methods: Electronic searches were performed using the Cochrane Controlled Trials Register, Medline, EMBASE, Cinahl and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved vs. same/worse.

Results: Prokinetics [14 trials, 1053 patients; relative risk reduction (RRR), 48%; 95% confidence interval (95% CI), 27–63%] and histamine‐2 receptor antagonists (11 trials, 2164 patients; RRR, 22%; 95% CI, 7–35%) were significantly more effective than placebo. Bismuth salts (RRR, 40%; 95% CI, − 3% to 65%) were superior to placebo, but this was of marginal statistical significance. Antacids and sucralfate were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic and histamine‐2 receptor antagonist results could be due to publication bias.

Conclusions: The meta‐analyses suggest that histamine‐2 receptor antagonists and prokinetics are superior to placebo. These data are difficult to interpret, however, as funnel plot asymmetry suggests that the magnitude of the effect could be due to publication bias or other heterogeneity‐related issues.
Review article: oral, modified‐release mesalazine formulations — proprietary versus generic
Authors: Forbes A. , Cartwright A. , Marchant S. , Mcintyre P. , Newton M.
Published: May 2003

Products containing mesalazine have been used in the treatment of inflammatory bowel disease for many years. Many of the oral, modified‐release products are reaching the point of patent expiration, and it is expected that several new ‘generic’ versions will be developed. As mesalazine acts topically, the drug needs to be available at the site of inflammation to be effective. For this reason, the currently available products have been developed with individual formulations so that physicians have a choice when matching the different release profiles to the site and extent of disease. As such, the current guidelines state that oral, delayed‐release mesalazine formulations are not interchangeable and should be prescribed by their proprietary (brand) name.

The standard regulatory assessment process for generic or ‘copy’ products, using systemic bioequivalence data, does not appear to be sufficient when evaluating topically acting, oral, modified‐release products. We therefore recommend that the regulatory bodies should require that new, oral mesalazine products should be assessed by a combination of dissolution, bioequivalence and (a minimum of one) adequately powered, comparative trial to determine therapeutic equivalence. Of most importance here is that the assessment of new modified‐release products is sufficiently rigorous to allow patients and physicians to be confident in their use.
Clinical usefulness of KRAS mutational analysis in the diagnosis of pancreatic adenocarcinoma by means of endosonography‐guided fine‐needle aspiration biopsy
Authors: Pellisé M. , Castells A. , Ginès A. , Solé M. , Mora J. , CastellvÍ‐Bel S. , Rodríguez‐Moranta F. , Fernàndez‐Esparrach G. , Llach J. , Bordas J. M. , Navarro S. , Piqué J. M.
Published: May 2003

Aim : To establish the usefulness of KRAS mutational analysis in the diagnosis of pancreatic adenocarcinoma by comparing this technique with conventional cytology in aspirates obtained by endosonography‐guided fine‐needle aspiration.

Methods : All consecutive patients with pancreatic focal lesions undergoing endosonography‐guided fine‐needle aspiration were included. Samples were obtained with the concourse of an attendant cytopathologist. Detection of codon‐12 KRAS mutations was performed by the restriction fragment length polymorphism‐polymerase chain reaction method. The effectiveness of conventional cytology, KRAS mutational analysis and their combination was established with respect to the definitive diagnosis. A cost‐effectiveness analysis was also performed.

Results : Thirty‐three patients had pancreatic adenocarcinoma and 24 patients had other lesions. A total of 136 samples was obtained. In patients in whom specimens were adequate (93% for cytology; 100% for mutational analysis), the specificity of both techniques was 100%, whereas the sensitivity favoured cytology (97% vs. 73%). When inadequate samples were considered as misdiagnosed, a combination of both techniques reached the highest overall accuracy (cytology, 91%; mutational analysis, 84%; combination of both, 98%).

Conclusions : Cytology from aspirates obtained by endosonography‐guided fine‐needle aspiration is the most precise single technique for the diagnosis of pancreatic adenocarcinoma. However, when adequate specimens are not available to reach a cytological diagnosis, the addition of KRAS mutational analysis represents the best strategy.
Meta‐analysis: evaluation of adjuvant therapy after curative liver resection for hepatocellular carcinoma
Authors: Mathurin P. , Raynard B. , Dharancy S. , Kirzin S. , Fallik D. , Pruvot F.‐R. , Roumilhac D. , Canva V. , Paris J.‐C. , Chaput J.‐C. , Naveau S.
Published: May 2003

Aim : To evaluate adjuvant modalities after curative resection for hepatocellular carcinoma using a meta‐analysis of randomized and non‐randomized controlled trials.

Methods : In a first step, a meta‐analysis of randomized controlled trials was carried out. Sensitivity analyses after inclusion of non‐randomized controlled trials were performed. Four therapeutic modalities were evaluated: pre‐operative transarterial chemotherapy, post‐operative transarterial chemotherapy, systemic chemotherapy and a combination of systemic and transarterial chemotherapy.

Results : Only post‐operative transarterial chemotherapy improved survival significantly at 2 years [difference, 22.8%; confidence interval (CI), 8.6–36.9%; P = 0.002] and 3 years (difference, 27.6%; CI, 8.2–47.1%; P = 0.005), and decreased the probability of no recurrence at 1 year (difference, 28.8%; CI, 16.7–40.8%; P < 0.001), 2 years (difference, 27.6%; CI, 8.2–47.1%; P = 0.005) and 3 years (difference, 28%; CI, 8.2–47.9%; P = 0.006). In a sensitivity analysis after inclusion of non‐randomized controlled trials, post‐operative transarterial chemotherapy still improved survival at 1 year (difference, 9.6%; CI, 0.8–18.3%; P = 0.03), 2 years (difference, 13.5%; CI, 0.9–26%, P = 0.04) and 3 years (difference, 18%; CI, 7–28.9%; P < 0.001), and decreased the probability of no recurrence at 1 year (difference, 20.3%; CI, 7.7–33%; P = 0.002), 2 years (difference, 35%; CI, 21.4–46.3%; P < 0.001) and 3 years (difference, 34.5%; CI, 18.7–50.3%; P < 0.001).

Conclusion : Post‐operative transarterial chemotherapy improved survival and decreased the cumulative probability of no recurrence. New randomized controlled trials evaluating this modality are required.
Meta‐analysis: proton pump inhibitor or H2‐receptor antagonist for Helicobacter pylori eradication
Authors: Graham D. Y. , Hammoud F. , El‐Zimaity H. M. T. , Kim J. G. , Osato M. S. , El‐Serag H. B.
Published: May 2003

Aim : To compare H2‐receptor antagonists and proton pump inhibitors as adjuvants to triple therapy for Helicobacter pylori eradication.

Methods : H. pylori‐infected patients with peptic ulcer were randomized to receive either 300 mg nizatidine or 30 mg lansoprazole plus 1 g amoxicillin and 500 mg clarithromycin taken b.d. for 7 days. H. pylori eradication was assessed 4 weeks after therapy. Using meta‐analytical techniques, we combined the results of this study with other randomized controlled comparisons of H2‐receptor antagonists and proton pump inhibitors as adjuvants to triple therapy.

Results : One hundred and one patients were randomized. H. pylori eradication was 94% (47/50) [95% confidence interval (CI), 83–99%] (intention‐to‐treat) in the H2‐receptor antagonist group vs. 86% (44/51) (95% CI, 74–94%) in the proton pump inhibitor group (P = 0.3). There has been a total of 12 similar studies (1415 patients). The overall efficacy was similar in intention‐to‐treat analysis: 78% (549/701) with H2‐receptor antagonists vs. 81% (575/714) with proton pump inhibitors (odds ratio, 0.86; 95% CI, 0.66–1.12). A non‐significant trend favouring H2‐receptor antagonist (79% vs. 69%; odds ratio, 1.14; 95% CI, 0.76–1.71; P = 0.5) was seen in the comparison of clarithromycin‐containing regimens. In contrast, in non‐clarithromycin‐containing trials, there was a slight, but significant, advantage with proton pump inhibitors (85% vs. 78%; odds ratio, 0.64; 95% CI, 0.45–0.92; P = 0.02).

Conclusion : Overall, proton pump inhibitor andH2‐receptor antagonist antisecretory agents appear to be similarly effective as adjuvants for H. pylori triple therapy. It is unlikely that the direct anti‐H. pylori effect of proton pump inhibitors is responsible for their ability to enhance anti‐H. pylori therapy.
An inter‐ and intra‐laboratory comparison of breath 13CO2 analysis
Authors: Perri F. , Zagari R. M. , Uebersax J. S. , Quitadamo M. , Bazzoli F. ,   The Helicobacter Pylori Sige Study Group on CO Measurement Standardization
Published: May 2003

Background:  13C breath test analysis requires accurate 13CO2 measurements.

Aim:  To perform a multicentre study to evaluate the repeatability and reproducibility of breath 13CO2 analysis.

Methods:  Two series of 25 paired randomly coded tubes (each consisting of 23 13CO2‐enriched breath samples and two samples of standard reference pure CO2 with certified δ13CPDB) were sent to participating centres for 13CO2 measurement. Each series of tubes was analysed 10 days apart. The repeatability and reproducibility of 13C measurements was assessed by Mandel's k and h statistics.

Results:  Twenty‐two centres participated in the study: 18 showed good inter‐ and intra‐laboratory variability, whilst four showed abnormally high inter‐ or intra‐laboratory variability. Breath test results were also significantly affected by the accuracy of the 13C analytical procedures.

Conclusions:  A low accuracy of 13C measurements may significantly affect the results of breath tests, leading to inappropriate clinical decisions. Standardization of 13C analysis is required to guarantee optimal 13C measurements and accurate 13C breath test results.
Current practice in surveillance strategy for patients with Barrett's oesophagus in the UK
Authors: Mandal A. , Playford R. J. , Wicks A. C.
Published: May 2003

Background:  Many guidelines exist regarding the surveillance of patients with Barrett's oesophagus. There are limited data, however, with regard to whether practitioners follow these guidelines.

Methods:  We assessed current surveillance practice amongst members of the British Society of Gastroenterology using a simple 11‐question anonymized survey, mailed to 300 randomly selected members from the British Society of Gastroenterology Handbook.

Results : Two hundred and three of the 300 (68%) responded, 76% considering that surveillance was worthwhile. In those who considered surveillance to be worthwhile, 83% used sub‐selection based on age, the length of Barrett's oesophagus or the presence of ulcer or stricture. Patients with Barrett's oesophagus of < 3 cm (short‐segment) were considered to be inappropriate for surveillance by 62%. Forty‐one per cent reported following the ‘advised’ recommendations of four‐quadrant biopsies every 2 cm, whereas 44% followed a ‘random and suspicious areas only’ protocol. Marked variation was reported in the re‐endoscope interval for both low‐ and high‐grade dysplasia. Only 55% reported that two experienced pathologists reviewed all biopsies showing high‐grade dysplasia.

Conclusions:  Despite the existence of multiple guidelines for Barrett's surveillance, clinical practice varies widely in the UK. This may be due to a lack of knowledge or because gastroenterologists remain unconvinced by the quality of the current evidence of its value. These results have implications for studies attempting to collate data from multiple centres.
The burden of illness of gastro‐oesophageal reflux disease: impact on work productivity
Authors: Dean B. B. , Crawley J. A. , Schmitt C. M. , Wong J. , Ofman J. J.
Published: May 2003

Background:  The impact of gastro‐oesophageal reflux disease on work productivity has become increasingly important, as the symptoms of gastro‐oesophageal reflux disease affect individuals in their productive years of life.

Aims:  To assess the impact of gastro‐oesophageal reflux disease on reduced work productivity and to identify the predictors of reduced productivity.

Methods:  A sample of employed individuals reporting chronic heartburn was selected from US household mail survey respondents. Heartburn severity and frequency were recorded using a diary, and work productivity was assessed using the Work Productivity and Activity Impairment Questionnaire for Patients with Symptoms of Gastro‐oesophageal Reflux Disease. Predictors of reduced productivity were evaluated.

Results:  Over 30% of heartburn sufferers reported reduced productivity. Individuals with symptoms of gastro‐oesophageal reflux disease (n = 1003) reported 6.0% reduced productivity attributable to symptoms. Over 48% of respondents with severe symptoms reported reduced productivity, compared with 40% and 12% of respondents with moderate and mild symptoms, respectively. Using logistic regression, severity, a younger age and nocturnal symptoms were associated with increased odds of reduced productivity. In those reporting nocturnal heartburn, medication use and sleep interference increased the odds of reduced productivity.

Conclusions:  Reduced work productivity is seen in a large proportion of subjects on prescription medication for gastro‐oesophageal reflux disease. Symptom severity and nocturnal heartburn are significantly associated with reduced work productivity, particularly when nocturnal heartburn interferes with sleep.
A prognostic model for survival in chronic lymphocytic leukaemia based on p53 expression
Authors: Giles Francis J. , Bekele B. Nebiyou , O'Brien Susan , Cortes Jorge E. , Verstovsek Srdan , Balerdi Maria , Yared Marwan , Zhou Xian , Kantarjian Hagop M. , Keating Michael J. , Thall Peter , Albitar Maher
Published: May 2003

Summary. As the abnormal expression of p53 protein is prognostically significant in some human cancers, its significance in patients with B‐cell chronic lymphocytic leukaemia (CLL) was assessed. Two investigators evaluated the percentage of bone marrow mononuclear cells that stained for p53, using biopsies stained with anti‐p53 monoclonal antibody (DO‐7), and graded the degree of staining (0, +, ++, +++). Samples from a cohort of 90 patients with CLL were studied (median age 60 years, range 30–89 years; 57 patients were (63%) previously untreated, 22 patients (24%) had received one or two prior regimens, 11 patients had received (12%) three to seven regimens. The overall percentage of cells positive for p53 staining was a median of 43 (range 1–88). No investigator effect was detected either in overall percentage cells rated p53 positive or on the degree of staining (Pearson's correlation coefficient 0·980, P‐value < 0·001). A Cox proportional hazards model showed that the percentage of ++ and +++ p53‐positive cells correlated with various prognostic factors in CLL (P < 0·0001). A multivariate model incorporating prior therapy, Rai stage, beta2 microglobulin (β2M) and p53 expression showed that only the percentage of p53‐positive cells and β2M were predictive of survival, and enabled the development of a highly predictive model of survival based on these two parameters.
Oxidative stress is involved in hydroxyurea‐induced erythroid differentiation
Authors: Nagai Tadashi , Tarumoto Takahisa , Miyoshi Takuji , Ohmine Ken , Muroi Kazuo , Komatsu Norio , Sassa Shigeru , Ozawa Keiya
Published: May 2003

Summary. Hydroxyurea (HU), an inhibitor of DNA synthesis, can also induce haemoglobinization in certain erythroid cell lines. In this study, we report that intracellular peroxides levels were increased in HU‐treated murine erythroleukaemia (MEL) cells and that l‐acetyl‐N‐cysteine (LNAC), a potent reducing reagent, had a significant inhibitory effect on the HU‐mediated induction of β‐globin, δ‐aminolaevulinate synthase mRNA expression and haemoglobinization of MEL cells. In contrast, the addition of LNAC to dimethyl sulphoxide (DMSO)‐treated MEL cells had a much smaller effect on the number of haemoglobinized cells. These findings suggest that oxidative stress is involved in HU‐mediated induction of erythroid differentiation and that HU induces MEL cell differentiation by a mechanism different to that involved in DMSO‐mediated differentiation. Our findings also suggest that the induction of MEL cell differentiation by HU does not involve RAS‐MAP (mitogen‐activated protein) kinase signalling.
Immunoplatelet counting: potential for reducing the use of platelet transfusions through more accurate platelet counting
Authors: Norris Scott , Pantelidou Despina , Smith Dan , Murphy Michael F.
Published: May 2003

Summary. Research is required to determine the optimal approach for prophylactic platelet transfusions in patients with haematological malignant disorders. It has been suggested that thresholds for prophylactic platelet transfusions of platelet counts below 10 × 109/l should be investigated, as these may be equivalent in clinical effectiveness and associated with lower costs and fewer complications. An important concern in such investigation is the accurate estimation of platelet counts below 10 × 109/l. This study aimed to further examine the potential reduction in platelet usage that could be made if a lowered platelet transfusion threshold of 5 × 109/l was used in conjunction with an immunoplatelet counting method. Clinical and laboratory data from 130 haematology patients were used. Standard platelet counting was performed using Bayer H3 and ABX Argos analysers. Immunoplatelet counting was performed by flow cytometry using anti‐CD61. The potential for reducing platelet transfusions included consideration of clinical criteria that influence prophylactic platelet transfusion use. The results indicated that the use of an immunoplatelet count with a 5 × 109/l platelet transfusion threshold would potentially reduce the number of transfusions by 10·4% in comparison with a 10 × 109/l threshold and standard automated platelet counting with the ABX Argos analyser, and increase the number of transfusions by 5·4% in comparison with the same threshold using the Bayer H3 analyser. The immunoplatelet count may aid the clinical decision to transfuse platelets, but would not necessarily lead to a reduced use of platelet transfusions.
Recombinant human macrophage colony‐stimulating factor‐induced thrombocytopenia in dogs
Authors: Abrams Kraig , Yunusov Murad Y. , Slichter Sherrill , Moore Peter , Nelp Wil B. , Burstein Samuel A. , McDonough Sean , Durack Lawrence , Storer Barry , Storb Rainer , Gass M. John , Georges George , Nash Richard A.
Published: May 2003

Summary. To characterize recombinant human macrophage‐colony stimulating factor (rhM‐CSF)‐associated thrombocytopenia (TCP), in vivo studies were performed in dogs, including the biodistributions and recoveries of radiolabelled autologous and allogeneic platelets. rhM‐CSF induced a reversible, dose‐dependent decrease in platelet counts. The number of megakaryocytes in spleen and marrow of rhM‐CSF‐treated dogs was increased two to threefold. Recoveries of allogeneic platelets transfused from rhM‐CSF‐treated donors into tolerized recipients (n = 3) were not significantly different from allogeneic baseline studies (93 ± 10% of baseline values at 24 h and 90 ± 1% at 40 h), whereas autologous platelets infused back into rhM‐CSF‐treated donors had decreased recoveries (45 ± 2% of baseline values at 24 h, P = 0·03 and 20 ± 4% at 40 h, P = 0·001). Platelet biodistribution studies showed increased accumulation of radiolabelled platelets over the spleens and livers of rhM‐CSF‐treated dogs. Histochemistry showed increased levels of platelet‐specific antigen (CD41; glycoprotein IIb) associated with Kupffer cells. The sensitivity of platelets from rhM‐CSF‐treated dogs to activation from thrombin, as measured by expression of P‐selectin (CD62P), was not significantly different when compared with baseline studies (P = 0·18; n = 4). These results support the concept that rhM‐CSF induces an activation of the monocyte–macrophage system (MMS), which causes a reversible TCP in a dog model.
Interleukin‐1 genotype and outcome of unrelated donor bone marrow transplantation
Authors: MacMillan Margaret L. , Radloff Gretchen A. , DeFor Todd E. , Weisdorf Daniel J. , Davies Stella M.
Published: May 2003

Summary.The interleukin 1 (IL‐1) gene family includes three members (IL‐1‐α, IL‐1‐β and IL‐1Ra) that mediate immune and inflammatory responses through two specific cell surface receptors. Cytosine to thymine transitions at codons −889 and −511 in the IL‐1‐α and IL‐1‐β genes, respectively, and an 86‐base pair repeat in the IL‐1Ra are believed to influence gene transcription. We have genotyped these three polymorphisms in 90 donor/recipient pairs undergoing unrelated donor bone marrow transplantation (BMT) at the University of Minnesota. We found no association between the occurrence of acute GVHD and donor and/or recipient polymorphisms of any of the three IL‐1 genes. The presence of at least one IL‐1α− 889 T allele in the donor was associated with significantly improved survival in univariate analysis (survival at 1 year 40% C/C donor, 68% T/C donor, 75% T/T donor,P < 0·01). Multiple regression analysis showed that if the donor and recipient each possessed the IL‐1α T allele there was significantly improved survival [relative risk (RR) 0·2,P < 0·01] and decreased treatment‐related mortality (TRM; RR 0·2,P = 0·01). The presence of the IL‐1β T allele in donor and recipient was also associated with improved survival (RR 0·2,P < 0·01) and decreased TRM (RR 0·1,P < 0·01). These data suggest that donor polymorphism in IL‐1α and IL‐1β might influence survival after unrelated donor BMT, but does not alter risk of GVHD.
Recombinant humanized anti‐CD40 monoclonal antibody triggers autologous antibody‐dependent cell‐mediated cytotoxicity against multiple myeloma cells
Authors: Hayashi Toshiaki , Treon Steven P. , Hideshima Teru , Tai Yu‐Tzu , Akiyama Masaharu , Richardson Paul , Chauhan Dharminder , Grewal Iqbal S. , Anderson Kenneth C.
Published: May 2003

Summary. Multiple myeloma (MM) is currently incurable, and novel therapies are needed. In this study, we examined a novel recombinant humanized monoclonal antibody against CD40 (rhuCD40 mAb) and demonstrate for the first time that rhuCD40 mAb induces antibody‐dependent cell‐mediated cytotoxicity (ADCC) against CD40‐positive MM cells. Importantly, we show that rhuCD40 mAb induces autologous ADCC against primary patient MM cells, without triggering ADCC against normal B cells. This study, therefore, both demonstrates that rhuCD40 mAb triggers autologous ADCC against patient MM cells and provides the framework for the clinical evaluation of rhuCD40 mAb immunotherapy to improve patient outcome in MM.
Localized non‐Hodgkin's lymphoma with B‐cell histology: cure without cyclophosphamide? A report of the United Kingdom Children's Cancer Study Group on studies NHL 8501 and NHL 9001 (1985–1996)
Authors: Amos Burke G. A. , Imeson John , Hobson Rachel , Gerrard Mary
Published: May 2003

Summary. We have examined the outcome for children treated on two consecutive United Kingdom Children's Cancer Study Group studies of localized B‐cell non‐Hodgkin's lymphoma (NHL). The first study (NHL 8501; 1985–1989) included cyclophosphamide in the treatment regimen at a total cumulative dose of 4 g/m2 whereas the regimen in the succeeding study (NHL 9001; 1990–1996) did not include cyclophosphamide. Ninety children with confirmed B‐cell NHL were treated in the two studies (NHL 8501, n = 33 and NHL9001, n = 57). With a median follow‐up of 7·5 years, overall survival for localized B‐cell NHL did not differ between the two regimens with observed 3‐year survivals of 94%[95% confidence interval (CI) 80–98%] and 89% (95% CI 79–95%) respectively (P = 0·47). There was also no difference in the event‐free survival between children treated on regimen NHL 8501 and NHL 9001 [91% (95% CI 76–97%) vs 84% (95% CI 73–92%) after 3 years; P = 0·34]. Although the difference in the number of failed remissions between NHL 8501 and 9001 (0/33 vs 6/57) approached statistical significance (P = 0·08, Fisher's exact test), there was no overall statistical difference between the treatment failures on either regimen (P = 0·34). Substantial long‐term survival can be achieved for many children with localized B‐cell NHL without the use of cyclophosphamide. Further studies are needed to identify whether all clinical or histopathological subgroups will benefit equally from the omission of cyclophosphamide.
The role of P‐selectin in the immune destruction of platelets
Authors: Turner Craig P. , Hadley Andrew G.
Published: May 2003

Summary. Antibody‐mediated platelet destruction is a poorly understood process, although several lines of evidence suggest that Fcγ receptor (FcγR)‐expressing splenic macrophages may be involved. In this study, chemiluminescence (CL) was used to measure the in vitro metabolic response of human monocytes to platelets sensitized with a human immunoglobulin (Ig)G1 recombinant antihuman platelet antigen‐1a (anti‐HPA‐1a) antibody (B2G1; P‐hrIgG1). CL responses were inhibited, but not abrogated, in the presence of 10 µg/ml human IgG or murine IgG2a, suggesting that FcγRI was principally involved. Experiments to determine the effect of Fab fragments to FcγRII found that CL responses to P‐hrIgG1 were significantly enhanced, indicating that crosslinking of monocyte FcγRII by platelet‐bound hIgG may modulate concomitant activation by FcγRI. Several observations suggested that the CL responses to P‐IgG were dependent on the activation of resting platelets during their co‐culture with monocytes and their subsequent P‐selectin‐mediated adhesion. First, the magnitude of the CL response was related to the level of P‐selectin expression following platelet activation with α‐thrombin. Second, CL responses were inhibited in the presence of antibodies that block the binding of P‐selectin to P‐selectin glycoprotein ligand‐1 but not when platelets were pretreated and then washed. Third, the addition of anti‐HPA‐1a to monocytes from HPA‐1a‐negative donors preincubated with HPA‐1a‐positive platelets resulted in rapid CL responses. Finally, PGI2 inhibited the CL response to resting P‐hrIgG1. Thus, evidence is presented that the interaction of human monocytes with P‐hrIgG1 is mediated by FcγRI, modulated via FcγRII, and enhanced by the presence of P‐selectin on the platelet membrane.
Lupus anticoagulant associated with transient severe factor X deficiency: a report of two patients presenting with major bleeding complications
Authors: Ashrani Aneel A. , Aysola Agnes , Al‐Khatib Hani , Nichols William L. , Key Nigel S.
Published: May 2003

Summary. Acquired factor X (FX) deficiency is rare, but has been reported in diverse disease states, including systemic amyloidosis and respiratory infections. FX deficiency associated with lupus anticoagulant (LA) and a bleeding diathesis has not been previously reported. We report two patients both of whom presented with a severe bleeding diathesis after a preceding respiratory infection due to isolated FX deficiency associated with a LA. The FX deficiency and LA were transient. We conclude that patients with LA may rarely present with severe acquired FX deficiency. This may be another mechanism whereby patients with antiphospholipid antibodies present with bleeding complications.