bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-analyses involving cluster randomization trials: a review of published literature in health care
Authors: Laopaiboon M
Published: November 2003

Throughout the 1980s and 1990s cluster randomization trials have been increasingly used to evaluate effectivenessof health care intervention. Such trials have raised several methodologic challenges in analysis. Meta-analyses involving cluster randomization trials are becoming common in the area of health care intervention. However, as yet there has been no empirical evidence of current practice in the meta-analyses. Thus a review was performed to identify and examine synthesis approaches of meta-analyses involving cluster randomization trials in the published literature. Electronic databases were searched for meta-analyses involving cluster randomization trials from the earliest date available to 2000. Once a meta-analysis was identified, papers on the relevant cluster randomization trials included were also requested. Each of the original papers of cluster randomization trials included was examined for its randomized design and unit, and adjustment for clustering effect in analysis. Each of the selected meta-analyses was then evaluated as to its synthesis concerning clustering effect. In total, 25 eligible meta-analyses were reviewed. Of these, 15 meta-analyses reported simple conventional methods of the fixed-effect model as method of analysis, while six did not incorporate the cluster randomization trial results in the synthesis methods but described the trial results individually. Three meta-analyses attempted to account for the clustering effect in the synthesis methods but approaches were in arbitrary. Fifteen meta-analyses included more than one cluster randomization trial, each of which included cluster randomization trials with a mixture of randomized designs and units, and units of analysis. These mixture situations might increase heterogeneity, but have not been considered in any meta-analysis. Some methods dealing with a binary outcome for some specific situations have been discussed. In conclusion, some difficulties in the quantitative synthesis procedures were found in the meta-analyses involving cluster randomization trials. Recommendations in the applications of approaches to some specific situations in a binary outcome variable have also been provided. There are still, however, several methodologic issues of the meta-analyses involving cluster randomization trials that need to be investigated further.
Steamrollered in Galicia: The Austro-Hungarian Army and the Brusilov Offensive, 1916
Authors: Schindler John
Published: November 2003

Russia’s summer 1916 Galician operation, the noted Brusilov offensive, was one of the most successful efforts of the First World War, resulting in the near-destruction of the Austro-Hungarian Army in the east. However, the causes of Russian success, and particularly of Habsburg defeat, have been little studied and less understood; in particular, ethnic-based disloyalty has always been the explanation for Austro-Hungarian setbacks in mid-1916. However, this article closely examines poor Habsburg battlefield performance, and concludes that serious tactical shortcomings and inadequate leadership, rather than the vexing nationalities’ question, were the true causes of Austro-Hungarian defeat at the hands of Alexei Brusilov’s offensive.
Common Doctrine Rather than Secret Staff Conversations: Military Co-operation between France and Switzerland in the 1920s and 1930s
Authors: Segesser Daniel Marc
Published: November 2003

Ever since the European Powers guaranteed Switzerland’s neutrality in 1815 the Swiss government and military leadership have always officially proclaimed to uphold its neutrality against any foreign interference. Nevertheless the development of Swiss military doctrine has always been strongly influenced by the military development in neighbouring countries, although Swiss officials would never have accepted such an influence publicly. The military authorities of neighbouring countries therefore had to rely on unofficial ways to influence the military development of Switzerland. While so far the focus has mainly been on secret staff conversations the article shows that personal contacts, public lectures and articles in Swiss military journals had a far greater impact on Swiss military doctrine than any secret conversations.
Military-Industrial Relations in Imperial Germany, 1870-1914
Authors: Epkenhans Michael
Published: November 2003

This article examines both the structure of the German armament industry and military-industrial relations in imperial Germany. As in other European countries, before 1914 the structure of the armament industry was mixed: state arsenals and naval dockyards on the one hand and private enterprises on the other hand supplied the armed forces with rifles, guns, and naval vessels. The relationship between the military and private enterprises, of which the Essen firm of Krupp was the most important one, was never really smooth. Whereas armaments were of little importance from a macroeconomic point of view, armament firms such as Krupp did, however, benefit from both the production and, especially, the export of arms, which was supported by the government in order to keep up a modern arms industry and to increase its influence in foreign countries.
The Politics of Strategy: Great Britain, Australia and the War against Japan, 1939-1945
Authors: Gooch John
Published: November 2003

An examination of the politico-strategic relationship between Great Britain and Australia during the Second World War demonstrates the extent to which wartime politics as conducted by Winston Churchill could be determined entirely by strategic logic. The basis for that logic was to be found in the plans and projections developed to control and manage the war against Japan. These plans, which rested on a strategic grammar composed partly of established working premises for gauging an enemy’s intentions and partly of more solidly based judgements about the range of military options open to the enemy, were of two kinds: until December 1941 they were speculative estimates of Japan’s likely course of action, while thereafter they became more robust calculations of her capabilities. Their influence shaped the wartime relationship between London and Canberra. It also explains the central paradox of the Anglo-Australian strategic relationship: that between January and June 1942, at the moment of greatest threat, Australia was least able to strike a military bargain with Great Britain on any terms which she could call her own.
Kriegsmarine and Luftwaffe Co-operation in the War against Britain, 1939-1945
Authors: Neitzel Sönke
Published: November 2003

The German contribution to the air war over the sea in the Second World War is associated with the great air-sea battles in the Mediterranean in 1941/42 and the Arctic in 1942. But hardly anything is known about the participation of the Luftwaffe in the battle in the Atlantic from the German perspective. This article illustrates the roots and the course of this important campaign and discusses the fundamental problems in the co-operation of the Luftwaffe with the navy. It shows that in peacetime the navy and during the war the Luftwaffe failed to recognize the importance of a well-planned inter-service co-operation in a theatre of war, where improvisation was hardly possible.
Asking Schlieffen: A Further Reply to Terence Zuber
Authors: Holmes Terence M.
Published: November 2003

This article continues the debate arising from Terence Zuber’s claim that the Schlieffen plan was written solely to demonstrate that the German army would be too weak for such an operation. I argue to the contrary that both variants of the Schlieffen plan are presented as workable strategies within the existing resources of the German army. The plan was based on the official deployment scheme for a one-front war, and the strong right-wing offensive through Belgium and into northern France was successfully rehearsed on the general staff ride of 1905. The article concludes by showing that the younger Moltke’s primary intentions in 1914 may also be seen as a version of the Schlieffen plan.
Service without Politics? Army, Militia and Volunteers in Britain during the American and French Revolutionary Wars
Authors: Cookson J. E.
Published: November 2003

A military that accepts the principle of state service ahead of political partisanship has long been an important feature of Britain’s political culture. Yet in the early eighteenth century the army’s loyalty to the state was confused by the personal authority and political proscriptions that George I and George II enforced. The raising of auxiliaries, commencing with the militia in 1757, also ran the risk of the politicization of military force. This article explores the detachment from politics that occurred in all cases in spite of the strong contentions that the American and French revolutions excited. The argument, in brief, is that the army defined itself as a service, the crown exercised restraint, the militia followed the example of the army, and the volunteers found an identity as defenders of the nation against the foreign enemy.
Undertaking the Role of Patient Advocate: a longitudinal study of nursing students
Authors: Altun Insaf , Ersoy Nermin
Published: November 2003

Patient advocacy has been claimed as a new role for professional nurses and many codes of ethics for nurses state that they act as patient advocates. Nursing education is faced with the challenge of preparing nurses for this role. In this article we describe the results of a study that considered the tendencies of a cohort of nursing students at the Kocaeli University School of Nursing to act as advocates and to respect patients’ rights, and how their capacities to do so changed (or not) as a result of their nursing education.

This longitudinal study used a questionnaire consisting of 10 statements relating to patient care. It was performed both at the start (1998) and at the end (2002) of the nursing training. At the beginning of their course 77 students participated; in the study. After four years, only 55 students participated, the reason for this drop in number being unknown.

The questions asked nurses if patients should have: the right to receive health care; the right to participate in the decision-making process about their treatment; the right always to be told the truth; and the right to have access to their own medical records. They were also asked: if quality of life should be a criterion for discontinuing treatment; if patients have the right to die and the right to refuse treatment; if patients should be assisted to die or helped to undergo active euthanasia; and if severely disabled newborn babies should be allowed to die. The student nurses demonstrated considerable insight into contemporary nursing issues and were ready to act as patient advocates. Professional responsibility demands that good nurses advocate strongly for patients’ choices.
The Death of a Patient with AIDS in Turkey: thoughts on the ethical dimensions
Authors: Namal Arin
Published: November 2003

A Turkish patient with AIDS attempted to commit suicide. Turkey is one of the countries where AIDS education in society and for health personnel has started rather late. This article documents what this patient, his sister and his friends, who helped him to survive for a short while, experienced in the hospital environment. This is a real case history and should be considered from various aspects because suicide was attempted by a person with AIDS who was near the terminal stage. The patient’s friends made a remarkable effort to help him to survive. They were unsure about what to do because they had not respected his wishes and they experienced deep alienation because of the extremely negative attitude of the medical staff.
The Use of Physical Restraints for Patients Suffering from Dementia
Authors: Weiner Chava , Tabak Nili , Bergman Rebecca
Published: November 2003

This study reviews the ethical dilemmas of nursing staff about using restraints on patients suffering from dementia in two types of health care settings in Israel: internal medicine wards of three general hospitals; and psychogeriatric wards of three nursing homes. The nurses’ level of knowledge about the Patient’s Rights Law, the Israeli Code of Ethics, and the guidelines on restraints was analysed. The purposes of restraints were defined as beneficial to: (1) the patient; (2) other patients; or (3) the institution. The concept was evaluated in a realistic situation (expressing views of daily practice) and in an idealistic situation (expressing personal and professional beliefs and values). It was shown that nurses in internal medicine wards of general hospitals agreed more with the use of restraints than those in psychogeriatric wards in nursing homes. Differences were more pronounced when restraints were beneficial to the institution. In addition, nurses working in psychogeriatric wards of nursing homes had more knowledge about the guidelines on restraints and were less inclined than their counterparts to agree with the use of restraints for the benefit of other patients or the institution.
Whistleblowing and Boundary Violations: exposing a colleague in the forensic milieu
Authors: Peternelj-Taylor Cindy
Published: November 2003

The purpose of this article is to examine the phenomenon of whistleblowing as it relates to a reconstructed case study of an erotic boundary violation that emerged from a clinical situation in forensic psychiatric nursing practice. The unique features of this case are illustrated with the help of a model for decision making. Although the ramifications of exposing a colleague are many, it is argued that, in this particular case, it was morally and ethically the right thing to do.
Nurses’ Ethical Conflicts in Performance of Utilization Reviews
Authors: Bell Sue Ellen
Published: November 2003

This article describes the ethical conflicts that a sample of US nurse utilization reviewers faced in their work, and also each nurse’s self-reported ethical orientation that was used to resolve the dilemmas. Data were collected from a sample of 97 registered nurses who were working at least 20 hours per week as utilization reviewers. Respondents were recruited from three managed care organizations that conduct utilization reviews in a large midwestern city. A cross-sectional survey design was used to collect demographic data and to ask closed-response, short-answer and open-ended questions. Ethical conflicts reported by nurses were similar across utilization review settings and many were justice orientated. Self-reported ethical orientations were similar across organizations, with beneficence dominating. Implications of these findings are discussed.
The Practice Setting: site of ethical conflict for some mothers and midwives
Authors: Thompson Faye E
Published: November 2003

Practitioners’ ethical orientation and responses vary between practice settings. Yet, currently, the ethics for midwifery practice that is explicit in the literature and which provides the ideals of socialization into practice, is that of bio(medical)ethics. Traditional bioethics, developed because of World War II atrocities and increased scientific research, is based on moral philosophy, normative theory, abstract universal principles and objective problem solving, all of which focus on right and wrong ‘action’ for resolving dilemmas. They exclude context and relationship.

Personal narratives of mothers and midwives contest the appropriateness of these accepted values and systems for childbirth because they induce conflict between work-place/service provider ethics and personal/professional midwifery ethics. In contrast to the disembedded and disembodied approach of biomedical ethics, an ethically adequate response in midwifery practice resonates more with the ethics of intimates, such as feminist virtue ethics.
Preserving Integrity: experiences of people with mental health problems living in their own home in a new neighbourhood
Authors: Granerud Arild , Severinsson Elisabeth
Published: November 2003

For patients with mental health problems, de-institutionalization has meant a shift from institutional care to living in the community. However, several studies show that problems of stigmatization, loneliness and negative attitudes devalue the dignity and autonomy of these patients. The aim of this study was to gain a deeper understanding of how people with mental health problems experience living in an apartment of their own. The data collection method was focus group interviews. The constant comparative method revealed the main category ‘preserving integrity’. The subcategories were: the need for control over information, similar relationships with both friends and neighbours (symmetrical contact), and ‘My home is my castle’. Participants who lived in a group home had little or no contact with their neighbours. The participants experienced lack of acceptance and loss of autonomy when meeting people. Integrity was a necessary condition in order for them to become equal citizens, experience autonomy and dignity, and have the opportunity to develop social contacts.
Korean Nurses’ Attitudes to Good and Bad Death, Life-Sustaining Treatment and Advance Directives
Authors: Kim Shinmi , Lee Yunjung
Published: November 2003

This study was an investigation of which distinctive elements would best describe good and bad death, preferences for life-sustaining treatment, and advance directives. The following elements of a good death were identified by surveying 185 acute-care hospital nurses: comfort, not being a burden to the family, a good relationship with family members, a readiness to die, and a belief in perpetuity. Comfort was regarded as the most important. Distinctive elements of a bad death were: persistent vegetative state, sudden death, pain and agony, dying alone, and being a burden to the family. Of the 185 respondents, 90.8% answered that they did not intend to receive life-sustaining treatment if they suffered from a terminal illness without any chance of recovery; 77.8% revealed positive attitudes toward advance directives. Sixty-seven per cent of the respondents stated that they were willing to discuss their own death and dying; the perception of such discussions differed according to the medical condition ( p = 0.001). The elements of a bad death differed significantly depending on the disease state ( p = 0.003) and on economic status ( p = 0.023).
Professional Values and Norms for Nurses in Belgium
Authors: Verpeet Ellen , Meulenbergs Tom , Gastmans Chris
Published: November 2003

Because of their responsibilities for providing high-quality care, at times when they are continuously confronted with inherent professional and ethical challenges, nurses should meet high ethical standards of practice and conduct. Contrary to other countries, where codes of ethics for nurses are formulated to support those standards and to guide nurses’ professional practice, Belgian nurses do not have a formal code of ethics. Nevertheless, professional ethics is recognized as an important aspect in legal and other professional documents. The aim of this article is to illustrate that codes of ethics are not the only professional documents reflecting nurses’ values, norms and responsibilities. Other documents can also set out professional nursing ethics, and as such replace codes of ethics.
The impact of workload changes and staff availability on IV chemotherapy services
Authors: Summerhayes Maxwell
Published: November 2003

Objectives. To determine the extent of change in intravenous (IV) chemotherapy workload in recent years, the availability of specialist pharmacy and nursing staff to carry out this work and the service implications of any mismatch between these two parameters. To determine the volume of chemotherapy currently administered for metastatic colorectal cancer (MCRC) to allow assessment of the possible workload implication of a switch to oral fluoropyrimidine therapy.

Design. An anonymous postal survey of pharmacist members of the British Oncology Pharmacy Association (BOPA) and their nursing colleagues.

Response. 0f 104 questionnaires distributed, 54 were returned (response rate 51.9%).

Data summary. Ninety-three per cent of pharmacists reported an increase averaging 178% (range 15]/500%) in the volume of IV chemotherapy being prepared by their units over the last five years, with the average unit currently producing 896 (range 110]/5000) doses each month. Pharmacist and nurse recruitment difficulties were also reported almost universally. The combination of these two factors led to reported problems for both staff and patients, with a majority of nursing and pharmacy staff noting increased staff stress and prolonged patient waiting times. A significant minority of departments have already taken, generally undesirable, steps to address a significant imbalance between chemotherapy workload and service capacity, including restricting clinical trial activity and other aseptic dispensing work.

Conclusions. Rapid expansion in the use of IV cytototoxic chemotherapy has resulted in pharmacy and nursing services facing severe pressure. Imaginative solutions are necessary if safe and efficient services are to be maintained. These may include increased use of oral fluorpyrimidines for the first-line treatment of MCRC, which this survey indicates accounts for about 10% of IV chemotherapy administered in the UK.
Clinical pharmacokinetics and metabolism of paclitaxel after a three-hour infusion: comparison of two preparations
Authors: Czejka Martin , Schueller Johannes , Schnait Heinz , Springer Beate , Eder Isabella
Published: November 2003

The clinical pharmacokinetics (PHK) of paclitaxel (PACLI) and its hydroxylated metabolites after three hours IV infusion (200 mg/m2) of two preparations were investigated in 13 patients receiving chemotherapy against breast cancer. Standard TaxolÒ was purchased from Bristol Myers Squibb and a test preparation ebetaxel (containing additional 2 mg/mL citric acid) was provided by Ebewe Pharma Austria. In the first cycle, either standard or test preparation was administered, then its alternative preparation in the second cycle (latin square, paired crossover design). In both treatment schedules the peak concentrations of PACLI occurred at the end of infusion after three hours. Mean peak concentration of PACLI was cmax5 505191131 ng/mL for the test preparation and cmax5 526991109 ng/mL for the standard preparation. No statistically significant differences in these plasma concentrations could be calculated. Mean tmax of metabolites was between 3.00 and 3.25 hours, their plasma concentrations were very similar: 6-OH-PACLI: cmax 4689266 ng/mL versus 4529212 ng/mL, 3Í-OH-PACLI: cmax 85938 ng/mL versus 90944 ng/mL, 3Í,6-DiOH-PACLI: cmax 87927 ng/mL versus 76931 ng/mL.

The PHK parameters of PACLI (AUC, Cltot, Vd) and its metabolites (AUC, t1/2 dis, t1/2 el) did not differ significantly between both preparations. Biotransformation of PACLI into its three hydro-xylated metabolites (expressed as their appearance in blood) was not affected by the content of citric acid in the test preparation.
Pyridoxine treatment and prevention of hand-and-foot syndrome in patients receiving capecitabine
Authors: Mortimer Joanne E , Lauman Mary Kay , Tan Benjamin , Dempsey Cindy L , Shillington Alicia C , Hutchins Kellie S
Published: November 2003

Background. Capecitabine is a novel fluoropyrimidine administered orally for treatment of gastrointestinal and breast malignancies. Toxicity described with capecitabine includes hand-and-foot syndrome (HFS), a potentially painful inflammation of the hands and feet. Pyridoxine has been reported to produce improvement in HFS symptoms. We conducted our study to determine the incidence and severity of HFS symptoms in capecitabine patients and to assess the effects of pyridoxine administered as prophylaxis or treatment.

Patients and methods. We retrospectively reviewed 99 charts of capecitabine patients receiving pyridoxine and 99 charts of those who had not.

Results. Of the 99 pyridoxine patients, 73 (74%) received it as prophylaxis, with the remainder receiving pyridoxine as acute HFS treatment. The median number of capecitabine cycles administered was five, with first-reported HFS onset at cycle 2 in those receiving pyridoxine prophylaxis versus 1.5 in those not (P 5 0.06). Incidence was significantly associated with capecitabine dose, with 76% of patients experiencing HFS in the highest dose ranges compared with 40% in the lowest (P B 0.01). The data did not support that pyridoxine prophylaxis prevented overall HFS incidence in a greater proportion of patients compared with those who did not receive prophylaxis (60% versus 53%, respectively, P 5 NS). However, when used as treatment, a greater proportion of patients receiving pyridoxine reported symptom improvement compared with those not receiving the agent (65% versus 12%, P B0.001). No differences in 12-week tumor response were seen.

Conclusion. The data do not support the use of pyridoxine as prophylaxis as neither the incidence nor the severity of HFS was affected. Once HFS develops, however, pyridoxine may provide some relief of HFS symptoms. A controlled trial of capecitabine with and without pyridoxine seems warranted.
Effects of combination therapy of beta-interferon 1a and prednisone on serum immunologic markers in patients with multiple sclerosis
Authors: Salama Hassan H , Kolar Oldrich J , Zang Ying CQ , Zhang Jingwu
Published: November 2003

Beta-interferon (beta-IFN) has a proven treatment effect on relapsing-remitting multiple sclerosis (MS), presumably through its regulatory properties on T-cell activation and cytokine production. This paper examines whether combination therapy of beta-IFN with prednisone would enhance immunoregulatory effects of beta-IFN by measuring serum levels of selected proinflammatory cytokines and soluble T-cell activation markers associated with MS. The selected markers were analyzed in MS patients treated with beta-IFN alone (n-22) and beta-IFN combined with a low daily dose of prednisone (n-33), as compared with those in 27 healthy controls at baseline and at a three-month interval for one year. The study confirmed that beta-IFN treatment inhibited serum levels of tumor necro sis factor-alpha (TNFa) and intracellular adhesion molecule-1 (IC A M-1) in patients with MS. However, combination therapy did not significantly enhance the inhibitory effect of beta-IFN treatment on the production of TNFa, interleukin (IL)-12, IL-2R, and IC A M-1, while the addition of prednisone antagonized the effect of beta-IFN on up-regulation of IL-10 and soluble C D95. No difference in the occurrence of binding antibodies to beta-IFN was found between the two treatment groups. The findings are important for the understanding of the role of combination therapy in the treatment of MS.
Effect of immunomodulatory drugs on in vitro production of brain-derived neurotrophic factor
Authors: Petereit H F , Lindemann H , Schoppe S
Published: November 2003

Multiple sclerosis (MS), a disease of presumably autoimmune aetiology, is character ized by inflammation, demyelination and axonal degeneratio n in the central nervous system. C urrent treatment concepts target the inflammatory activity, reducing the number of relapses and inflammatory lesions on magnetic resonance imaging as well as the proinflammatory cytokine production in blood lymphocytes. Recently, the neuroprotective aspect of inflammation has been documented and is thought to be mediated by neurotrophins, like brain-derived neurotrophic factor (BDNF). The question whether the in vitro BDNF production in MS patients and healthy controls is influenced by the immunomodulatory agents interferon beta (IFN-beta) and immunoglobulin G (Ig) is addressed. A significantly increased BDNF production in MS patients was found compared with normal controls (mean±SD: 492±172 pg/mL versus 217±55 pg/mL, P-0.001). IFN-beta and low-dose Ig had no effect on BDNF production, whereas high-dose Ig reduced in vitro BDNF production in MS patients significantly (to 409±125 pg/mL, P-0.001). These in vitro findings might indicate that Igs in high doses potentially interfere with neuroprotective mechanisms despite their potent anti-inflammatory properties.
The use of quality of life measures in multiple sclerosis research
Authors: Nortvedt M W , Riise T
Published: November 2003

Q uality of life research contributes knowledge essential to the health and healthcare of multiple sclerosis (MS) patients. This article reviews 83 MS studies in English that have presented data on quality of life. The studies may be classified into three categories, according to the application and the main focus: 1) evaluating the development and validity of quality of life questionnaires and clinical scales (n-27); 2) evaluating factors that might influence the quality of life or comparing the quality of life among various groups (n-37); and 3) using quality of life questionnaires as outcome measures in medical trials and other interventions (n-19). The studies have shown that quality of life questionnaires more broadly measure the impact of MS than do the most frequently used measures of disease activity and effects. Using quality of life measures provides additional information in evaluating the effects of treatment and in studying the development of the disease. Such information is crucial in planning interventions for MS patients. A challenge in this field is to improve the study designs, including reaching some agreement on how to measure the quality of life.
Gadolinium-enhanced magnetic resonance imaging predicts response to methylprednisolone in multiple sclerosis
Authors: Sellebjerg F , Jensen C V , Larsson H BW , Frederiksen J L
Published: November 2003

O ral high-dose methylprednisolone treatment is efficacious in acute optic neuritis (O N) and attacks of multiple sclerosis (MS). The responses to treatment in subgroups of patients participating in two randomized, controlled trials were assessed. Fifty-eight patients with O N and 51 patients with attacks of MS were treated with placebo or oral methylprednisolone (500 mg daily for five days with a 10-day tapering period). A gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) scan was obtained at baseline in 66 patients, and 29 patients underwent repeated MRI studies. Seventy-four patients underwent lumbar puncture before treatment. The odds ratio (O R) of improvement after methylprednisolone treatment (a one point change in the visual function system score of the Kurtzke Expanded Disability Status Scale (EDSS) in O N or in the EDSS score in attacks of MS) was higher in patients with enhancing lesions on baseline MRI (one week: O R 15, P-0.02; eight weeks: O R 4.6, P-0.02). Methylprednisolone treatment suppressed G d-enhancement after one week (P-0.001) and three weeks (P-0.001). C erebrospinal fluid measures of intrathecal inflammation correlated with the area of G d-enhancement but did not correlate as closely with the treatment response as did the results of G d-enhanced MRI. These findings suggest that the resolution of intrathecal inflammation as assessed by G d-enhanced MRI is a major effect of oral high-dose methylprednisolone.
Factors that predict Health-Related Q uality of Life in patients with relapsing -remitting multiple sclerosis
Authors: Miller Deborah M , Rudick Richard A , Baier Monika , Cutter Gary , Doughtery David S , Weinstock-Guttman Bianca , Mass Michele K , Fisher Elizabeth , Simonian Nancy
Published: November 2003

Health-Related Q uality of Life (HRQ oL) research is gaining acceptance in the field of multiple sclerosis (MS). Little is known about what precipitates quality of life change. It was hypothesized that physical aspects of quality of life decline with worsening objective disease measures and psychosocial aspects remain relatively stable regardless of change in objective measures. These assumptions are tested using data from a Phase 3 study of relapsing -remitting MS patients treated with interferon b-1a and reassessed approximately eight years after study initiation. The Sickness Impact Profile (SIP) questionnaire is the generic quality of life measure used in this study. Three summary scores of the SIP (Physical, Psychosocial, and Total scores), Expanded Disability Status Scores, Multiple Sclerosis Functio nal C omposite, and Brain Parenchymal Fraction were determined at baseline, year 2, and after an average of 8.1 years from study entry. SIP data collected during a clinic visit were available from 137 of the original 172 participants. A ll objective indicators worsened by follow-up. SIP Physical and Total scores significantly worsened from baseline to follow-up. SIP Psychosocial showed nonsignificant worsening. Regression analysis indicated that final measures of SIP Physical and Total scores were most strongly associated with change in objective measures and follow-up SIP Psychosocial was most strongly related to earlier scores on the same measure.
Validity of the Beck Depression Inventory-Fast Screen in multiple sclerosis
Authors: Benedict R HB , Fishman I , McClellan M M , Bakshi R , Weinstock-Guttman B
Published: November 2003

Introduction: The Beck Depression Inventory-Fast Screen (BDI-FS) is a brief self-report inventory designed to evaluate depression in patients with medical illness. A s depressive disorder is especially prominent in multiple sclerosis (MS), a cost-effective procedure for identifying depressive disorder in MS is sorely needed. The BDI-FS may be useful in this regard although, to date, its validity in MS patients has not been assessed. Methods: Fifty-four consecutive MS patients were studied. A ll underwent psychological assessment, which included the BDI-FS and other self-report measures of depression. Forty-eight caregiver/informants were interviewed using the Neuorpsychiatric Inventory (NPI). Retrospective chart reviews were conducted by a single trained research assistant, blind to the results of psychological testing and interviews, to determine if antidepressant medications had been prescribed. Results: The BDI-FS was significantly correlated with other self-report measures of depression (P B-0.001) and with informant reported dysphoria (P B-0.01), In addition, BDI-FS scores discriminated MS patients undergoing treatment for depressive disorder from untreated MS patients (P =0.01). Conclusion: These data support the concurrent and discriminative validity of the BDI-FS in MS. A s the test is brief and not confounded with neurological symptoms, it is recommended for depression screening in this population.
Increasing frequency of multiple sclerosis in Padova, Italy: a 30 year epidemiological survey
Authors: Ranzato F , Perini P , Tzintzeva E , Tiberio M , Calabrese M , Ermani M , Davetag F , De Zanche L , Garbin E , Verdelli F , Villacara A , Volpe G , Moretto G , Gallo P
Published: November 2003

Objective: To determine the incidence and prevalence rates of multiple sclerosis (MS) and their temporal profiles over the last 30 years in the province of Padova (northeast Italy). Background: In the early 1970s an epidemiological survey in the province of Padova showed a MS prevalence and incidence of 16/100 000 and 0.9/100 000 population, respectively; these figures are much lower than current estimates in other regions of Italy and C entral Europe. Methods: The population of the study area was approximately 820000 (422 028 women, 398290 men) in the 1991 census. A ll possible sources of case collection were used, but only clinically definite/probable and laboratory-supported definite/probable MS were considered in the analysis of incidence and prevalence trends from 1971 to 1999. Results: O n 31 December 1999, the crude prevalence rate was 80.5/100 000 (95% C I 70.3-90.7); prevalence was higher in women (111.1/100 000; 95% C I 99.0-123.1) than in men (49.7/100 000; 95% C I 41.3-58.1). This difference was significant (F/M=2.43; z=10.1, P B-0,00001); a rate adjusted for the European population was 81.4/100 000. O n 31 December 1980 and on 31 December 1990 the estimated prevalence rates were 18/100 000 and 45.7/100 000, respectively. Thus, a fivefold increase in prevalence was observed from the 1970s. The mean annual incidence was 2.2/100000 in the period 1980-89, 3.9 in the period 1990-94 and 4.2 in the period 1995-99. Thus, incidence increased more than fourfold from the 1970s through 1994 and remained quite stable in the last several years. Mean age at onset was 31.39-9.88 years. Mean diagnostic latency decreased significantly from 49.29-44.5 months in 1985 to 23.09-30.3 months in 1990, 12.99-15.61 in 1995 and 5.39-4.7 in 1999. Conclusions: The actual prevalence (80.5/100 000) and incidence (4.2/100000) of MS in the province of Padova agree with the most recent epidemiological estimates/trends observed in other Italian and European areas, except for Sardinia and Scotland. The increase in both incidence and prevalence rates observed in much of this region over the last 30 years parallels the introduction of more sensitive diagnostic techniques and a highly significant decrease in diagnostic latency. These findings probably do not support a real increase in the frequency of MS in northeast Italy because recent estimates of incidence have increased only slightly (3.9 to 4.2, which is B-10% in five years) and increase in the prevalence rate was almost completely due to the accumulatio n of new incidence cases.
Oral interferon beta-1a in relapsing-remitting multiple sclerosis: a double-blind randomized study
Authors: Polman C , Barkhof F , Kappos L , Pozzilli C , Sandbrink R , Dahlke F , Jakobs P , Lorenz A ,   European Oral Interferon Beta-1a in Relapsing-Remitting MS Study Group
Published: November 2003

Background: Interferon beta (IFNB) is available in parenter al formulations for treatment of multiple sclerosis (MS). The purpo se of this study was to evaluate safety, tolerability and effects on MRI lesions of three different doses of oral IFNB-1a compared with placebo over six months in relapsing-remitting (RR) MS patients. Methods: In this multicenter, double-blind randomized trial, RR -MS patients received 0.06, 0.6 or 6 million international units (MIU) IFNB-1a or placebo every other day for up to six months. G adolinium DTPA enhanced brain MRI scans were performed at screening and monthly during treatment. The primary variable was the cumulative number of newly active lesions. Secondary variables included volume of enhancing lesions on T1-weighted images each month and lesion volume on T2-weighted images at months three and six. Safety measures included adverse events, laboratory variables, vital signs, ECG, physical examination, EDSS and number of relapses. Neopterin was measured in 21 patients and neutralizing antibodies in 24 patients. Results: O f 194 screened patients, 173 were randomized (42-44 patients per group) in 15 centers. Median cumulative numbers of newly active lesions over six months were 4.0 in the placebo and 0.6 MIU groups, compared with 7.5 and 9.0 in the 0.06 and 6 MIU groups (no significant differences). Secondary efficacy endpoints showed small and inconsistent differences between groups. A dverse events showed no notable group differences. A pproximately two-thirds of patients in each group remained relapse free. No patients showed neutralizing antibodies. Neopterin levels were comparable between groups. Conclusion: O ral IFNB-1a showed neither beneficial effects in RRMS nor any systemic biological effects. Treatment was safe and well tolerated.
Refiexology treatment relieves symptoms of multiple sclerosis: a randomized controlled study
Authors: Siev-Ner I , Gamus D , Lerner-Geva L , Achiron A
Published: November 2003

Objective: To evaluate the effect of reflexology on symptoms of multiple sclerosis (MS) in a randomized, sham-controlled clinical trial. Methods: Seventy-one MS patients were randomized to either study or control group, to receive an 11-week treatment. Reflexology treatment included manual pressure on specific points in the feet and massage of the calf area. The control group received nonspecific massage of the calf area. The intensity of paresthesias, urinary symptoms, muscle strength and spasticity was assessed in a masked fashion at the beginning of the study, after 1.5 months of treatment, end of study and at three months of follow-up. Results: Fifty-three patients completed this study. Significant improvement in the differences in mean scores of paresthesias (P =0.01), urinary symptoms (P =0.03) and spasticity (P =0.03) was detected in the reflexology group. Improvement with borderline significance was observed in the differences in mean scores of muscle strength between the reflexology group and the controls (P =0.06). The improvement in the intensity of paresthesias remained significant at three months of follow-up (P =0.04). Conclusions: Specific reflexology treatment was of benefit in alleviating motor, sensory and urinary symptoms in MS patients
Safety and tolerability of cyclophosphamide ‘pulses’ in multiple sclerosis: a prospective study in a clinical cohort
Authors: Portaccio E , Zipoli V , Siracusa G , Piacentini S , Sorbi S , Amato M P
Published: November 2003

To assess the safety and tolerability of cyclophosphamide (C TX) ‘pulse’ therapy in progressive or very active multiple sclerosis (MS), we reviewed our experience in a cohort of MS patients who have been treated and prospectively followed-up in our Department since 1997. O ne hundred and twelve patients received intravenous C TX in monthly ‘pulses’ for 12 months at the dosage of 700 mg/m2 of body surface, then bimonthly for another 12 months. We evaluated the frequency and the severity of side-effects, as well as overall tolerability by the patient perspective using a visual analogue scale (VAS). Side-effects resulted in the discontinuation of therapy in 20 (18%) cases. Serious side-effects were observed in 24 patients (21.4%), most commonly definitive amenorrhea (33.3% of fertile women), hypogammaglobulinemia (5.4%), and hemorrhagic cystitis (4.5%). Malignancies were diagnosed in four (3.6%) subjects, three of whom were previously treated with azathioprine (AZA). Finally, 81.8% of the patients judged the treatment regimen as very or relatively acceptable and tolerable. O ur data point to a reasonable safety and tolerability of C TX ‘pulse’ therapy. Further trials are needed to definitively assess the efficacy of C TX as an alternative therapeutic option for progressive or very active MS.
Cognitive impairment in multiple sclerosis does not affect reliability and validity of self-report health measures
Authors: Gold Stefan M , Schulz Holger , Mönch Andrea , Schulz Karl-Heinz , Heesen Christoph
Published: November 2003

Patient self-report health measures have received increasing recognition as supplementar y outcome parameters in multiple sclerosis (MS). G iven the high prevalence of cognitive problems in this population, reliability and validity of self-report instruments in patient groups with cognitive impairment is essential, especially when using such scales longitudinally. A sample of 80 MS patients with cognitive dysfunction according to Symbol Digit Modalities Test (SDMT) score and 107 unimpaired patients were included in the analyses. Data was available from the Hamburg Q uality of Life Q uestionnaire in Multiple Sclerosis (HAQ UA MS), the Hospital A nxiety and Depression Scale (HA DS), clinical rating scores [Expanded Disability Status Scale (EDSS) and FS (Functio nal Status) scales, C A MBS (Cambridge MS Basic Score)] and objective tests of upper and lower limb function [Timed 8 Meter Walk (T8) and Nine Hole Peg Test (9HPT)). Both self-report questionnaires showed satisfactory internal consistencies and retest reliability. Pattern and magnitude of correlations with other health status measures supported the validity of both instruments. However, there was a marked discrepancy between subjective and objective measures of cognitive function. C ognitively impaired patients furthermore showed significantly higher depression and anxiety as well as lower quality of life (Q oL). The report provides evidence that Q oL and affective symptomatology can be reliably assessed in MS patients with cognitive dysfunction. The common pattern of poor correlation between self-rated and objective cognitive function thus appears to be a result of the patients’ (adaptive or maladaptive) coping mechanisms rather than being due to inaccurate measurement.
Hemeoxygenase-1 in SJL mice with experimental allergic encephalomyelitis
Authors: Chakrabarty A , Emerson M R , LeVine S M
Published: November 2003

The expression of heme oxygenase-1 (HO -1) is increased in the C NS of mice and rats with experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis (MS). To investigate the role of HO -1 in EAE, a putative inhibitor [tin-pro toporphyrin IX (Sn-PP IX)] of HO -1 was administered to SJL mice during active disease. Sn-PP IX (200 mmol/kg) attenuated clinical scores, weight loss, and some signs of patho logy in comparison to vehicle treatment. G lutathione levels were greater in treated EAE mice than in those receiving vehicle, indicating lower oxidative stress in the former group. These data suggest that inhibition of HO -1 attenuated disease and suppressed free radical production. In the SJL model of EAE, extravasated blood is present in the C NS, and iron released by HO -1 from this heme source may not be adequately sequestered by ferritin, allowing for iron-mediated tissue damage. Thus, HO -1 may act to amplify the disease process in this model.
Evidence-based measurement in multiple sclerosis: the psychometric properties of the physical and psychological dimensions of three quality of life rating scales
Authors: Riazi A , Hobart J C , Lamping D L , Fitzpatrick R , Thompson A J
Published: November 2003

The selection of measures of quality of life used in clinical trials of multiple sclerosis (MS) should be evidence-based. Head-to -head comparison of measures facilitates the selection of measures. The aim of the study was to compare the psychometric properties of the physical and psychological dimensions in three measures of quality of life to aid choice of the most appropriate scale for use in clinical trials of MS. O ne hundred and twenty-one people with MS (rehabilitation =57; steroids =64) completed a selection of health measures before and after treatment. The psychometric properties of three measures of physical function (MSIS-29 physical, SF-36 physical functioning, FA MS mobility) and three measures of psychological function (MSIS-29 psychological, SF-36 mental health, FA MS emotional well-being) were compared by examining data quality, scaling assumptions, acceptability, reliability, validity and responsiveness. Physical (0.63- 0.71) and psychological (0.70-0.75) scales were substantially correlated indicating they measure related constructs. The MSIS-29 physical and psychological scales satisfied all criteria for internal consistency reliability (physical =0.91; psychological =0.89) and validity. The SF-36 physical scale had a notable floor effect (20%). The FA MS mobility scale had lower reliability (a=0.78) compared to other measures. The MSIS-29 physical (effect size=0.91) and psychological (effect size =0.62) scales were the most responsive. In these three samples, the MSIS-29 had better measurement properties for combined physical and psychological health than the SF-36 and the FA MS.