bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost savings associated with improving appropriate and reducing inappropriate preventive care: cost-consequences analysis
Authors: Hogg William , Baskerville Neill , Lemelin Jacques
Published: March 2005

Background

Outreach facilitation has been proven successful in improving the adoption of clinical preventive care guidelines in primary care practice. The net costs and savings of delivering such an intensive intervention need to be understood. We wanted to estimate the proportion of a facilitation intervention cost that is offset and the potential for savings by reducing inappropriate screening tests and increasing appropriate screening tests in 22 intervention primary care practices affecting a population of 90,283 patients.

Methods

A cost-consequences analysis of one successful outreach facilitation intervention was done, taking into account the estimated cost savings to the health system of reducing five inappropriate tests and increasing seven appropriate tests. Multiple data sources were used to calculate costs and cost savings to the government. The cost of the intervention and costs of performing appropriate testing were calculated. Costs averted were calculated by multiplying the number of tests not performed as a result of the intervention. Further downstream cost savings were determined by calculating the direct costs associated with the number of false positive test follow-ups avoided. Treatment costs averted as a result of increasing appropriate testing were similarly calculated.

Results

The total cost of the intervention over 12 months was $238,388 and the cost of increasing the delivery of appropriate care was $192,912 for a total cost of $431,300. The savings from reduction in inappropriate testing were $148,568 and from avoiding treatment costs as a result of appropriate testing were $455,464 for a total savings of $604,032. On a yearly basis the net cost saving to the government is $191,733 per year (2003 $Can) equating to $3,687 per physician or $63,911 per facilitator, an estimated return on intervention investment and delivery of appropriate preventive care of 40%.

Conclusion

Outreach facilitation is more expensive but more effective than other attempts to modify primary care practice and all of its costs can be offset through the reduction of inappropriate testing and increasing appropriate testing. Our calculations are based on conservative assumptions. The potential for savings is likely considerably higher.
Making reconnections in agro-food geography: alternative systems of food provision
Authors: Watts D. C. H. , Ilbery B. , Maye D.
Published: March 2005

This article reviews recent research into alternative systems of food provision. It considers, first, what the concept of`alternativeness' might mean, based on recent discussions in economic geography. Informed by this, it discusses food relocalization and the turn to `quality' food production, arguing that both are `weaker' alternative systems of food provision because of their emphasis on food. It then examines some `stronger' alternative systems of food provision, which emphasize the networks through which food passes. Lastly, the paper reflects on the concept of alternativeness in the context of food supply chains, and suggests some possible directions for future research.
Skyscraper geography
Authors: McNeill Donald
Published: March 2005

This paper argues that geographers have tended to neglect the substantial impact of skyscrapers on urban life. Yet the significance of these buildings - in terms of height, levels of human occupancy, aesthetic impact and popular representation and use - is in need of careful geographical interpretation. Synthesizing work from a number of disciplines - geography, social history, architecture, planning, and cultural studies - it argues that the skyscraper is an extremely complex spatial phenomenon. First, the development and diffusion of skyscrapers as a global form is considered in terms of its geographical contingency, and the relational nature of its production. Secondly, the representational nature of the form in relation to cities is discussed, including attention to cinematic, biographical and everyday practices of representation. Thirdly, the volumetric nature of the skyscraper in urban form is briefly reviewed, focusing on its differing impacts on urban space and at various physical strata of the city. Taken together, there are important urban, political, social, cultural and economic debates that underpin this apparently regularized, rationalized built form.
Ways of relating: hospitality and the acknowledgement of otherness
Authors: Barnett Clive
Published: March 2005

This paper considers the relevance of the work of Emmanuel Levinas and Jacques Derrida to geography's engagements with both mainstream moral philosophy and poststructuralist theory. This relevance lies in the way in which their work unsettles the ascription of normative value to relations of proximity and distance. Distance is usually understood to be a medium of moral harm or indifference. In contrast, Levinas presents distance as the very condition of responsibility. Grasping the significance of this argument requires an appreciation of the temporality of responsibility and responsiveness that both Levinas and Derrida emphasize. They present an alternative way of understanding the relationality of subjectivity and social processes. Through a schematic exposition of key themes in Levinas' work, prevalent understandings of the spatiality of relations are shown to harbour their own forms of indifference and moral harm. The full effect of Levinas' reconsideration of the value of relations between proximity and distance is brought out in Derrida's recent writings on hospitality. For both thinkers, there is no natural geographical scene for the cultivation of responsibility. Rather, their shared focus upon temporality emphasizes the degree to which responsibility is motivated in response to the activities of others. The implication of this argument is that critical analysis should be reorientated towards practices that shape individual and collective dispositions to acknowledge the claims of others.
A double-blind, randomized, controlled study of oral pirfenidone for treatment of secondary progressive multiple sclerosis
Authors: Walker Jonathan E , Giri Shri N , Margolin Solomon B
Published: March 2005

Currently, there are no approved treatments for secondary progressive multiple sclerosis (MS) that stabilize or reverse the neurological disabilities associated with this disease. Oral pirfenidone was found to stabilize and overcome the disabilities in two published independent open-label studies in secondary progressive MS. This led us to study pirfenidone in a phase II double-blind, randomized and controlled, clinical trial in patients with advanced secondary progressive MS for 12 months. Forty-three patients met the eligibility criteria approved by the IRB and accepted by the FDA. Of these patients, 18 were randomly assigned to placebo and 25 patients to oral pirfenidone groups. All eligible patients were included in the statistical analysis of the data according to intention-to-treat principles. Some patients on oral pirfenidone manifested mild drug-related adverse effects, but it was well tolerated overall. By one month, pirfenidone significantly (P<0.05) improved the Scripps Neurological Rating Scale (SNRS) scores, and scores remained significantly improved for 3, 6 and 12 months when compared to the baseline SNRS scores. In contrast, the SNRS scores of patients on oral placebo were not significantly improved at 1, 3, 6 or 12 months of the study, when compared with baseline scores. Oral pirfenidone significantly (P<0.04) reduced the incidence of relapses (27.8% on placebo versus 8.0% on pirfenidone). Furthermore, oral pirfenidone treatment was associated with a marked improvement in bladder dysfunction (40.0% on pirfenidone versus 16.7% on placebo). Expanded Disability Status Scale scores and MRI lesion count were not significantly different in the placebo and pirfenidone groups. These findings indicate a significant effect of pirfenidone on clinical disability and bladder function for secondary progressive MS patients. A major multicentre, double-blind, randomized, controlled trial is justified.
Cost of multiple sclerosis by level of disability: a review of literature
Authors: Patwardhan M B , Matchar D B , Samsa G P , McCrory D C , Williams R G , Li T T
Published: March 2005

We performed a review of the economic literature to identify what is known about the relationship between Expanded Disability Status Scale (EDSS) categories and cost of multiple sclerosis (MS). We sought cohort studies of patients with multiple sclerosis that described the costs attributed to each EDSS score and utilized specific inclusion criteria for the selection of 10 studies. We found that both direct and indirect costs rise continuously with increasing EDSS category, and this rise is qualitatively exponential. The rise in indirect costs appears at lower EDSS scores. The cost of a relapse occurring in any given EDSS category exceeds that associated with that particular EDSS category. Few studies comprehensively assessed the entire spectrum of the costs, and much of the literature is based on EDSS categories in coarse groupings. In spite of several variations between studies, one important conclusion that we can draw is that rise in cost is positively correlated to scores on the EDSS categories, and therefore agents with a capacity to prevent or arrest the rate of MS progression may affect the overall cost of MS.
Lipoic acid in multiple sclerosis: a pilot study
Authors: Yadav V , Marracci G , Lovera J , Woodward W , Bogardus K , Marquardt W , Shinto L , Morris C , Bourdette D
Published: March 2005

Lipoic acid (LA) is an antioxidant that suppresses and treats an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis. The purpose of this study was to determine the pharmacokinetics (PK), tolerability and effects on matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecule-1 (sICAM-1) of oral LA in patients with MS. Thirty-seven MS subjects were randomly assigned to one of four groups: placebo, LA 600 mg twice a day, LA 1200 mg once a day and LA 1200 mg twice a day. Subjects took study capsules for 14 days. We found that subjects taking 1200 mg LA had substantially higher peak serum LA levels than those taking 600 mg and that peak levels varied considerably among subjects. We also found a significant negative correlation between peak serum LA levels and mean changes in serum MMP-9 levels (τ=-0.263, P=0.04). There was a significant dose response relationship between LA and mean change in serum sICAM-1 levels (P=0.03). We conclude that oral LA is generally well tolerated and appears capable of reducing serum MMP-9 and sICAM-1 levels. LA may prove useful in treating MS by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS.
Self-Injection Anxiety Training: a treatment for patients unable to self-inject injectable medications
Authors: Mohr David C , Cox Darcy , Merluzzi Natalia
Published: March 2005

Anxiety and phobia frequently prevent patients with multiple sclerosis (MS) from self-injecting their injectable disease-modifying medications. This small, randomized, controlled trial tested the efficacy of a six-session nurse-administered programme to teach self-injection to patients with MS, who, due to anxiety or phobia, were unable to self-inject their injectable medications. Participants were 30 patients with MS who were prescribed interferon beta-1a (IFNβ-1a) administered via weekly intramuscular injection. All patients were unable to self-inject due to anxiety or phobia. Patients were randomized to either the six-session Self-Injection Anxiety Therapy (SIAT) or a control telephone support condition modelled on the support programme offered by the manufacturer of IFNβ-1a. Four patients dropped out of SIATwhile three dropped out of the control condition. Eight patients receiving SIAT, compared to three control patients, were able to self-inject after six weeks of treatment. SIAT patients were significantly more likely to achieve self-injection at treatment cessation, compared to telephone control patients, in completer analyses (p=0.022), however, this only reached a trend in intent-to-treat analyses (p=0.058). These findings suggest that SIAT is a potentially valuable intervention to teach self-injection skills to injection phobic and anxious patients, and should be investigated more thoroughly in a larger clinical trial.
Discrepancies in the interpretation of clinical symptoms and signs in the diagnosis of multiple sclerosis. A proposal for standardization
Authors: Uitdehaag Bernard MJ , Kappos Ludwig , Bauer Lars , Freedman Mark S , Miller David , Sandbrink Rupert , Polman Chris H
Published: March 2005

The new McDonald diagnostic criteria for multiple sclerosis (MS) incorporate detailed criteria for the interpretation and classification of magnetic resonance imaging (MRI) findings, but, in contrast, provide no instructions for the interpretation of clinical findings. Because MS according to the McDonald criteria is one of the primary endpoints in a large trial enrolling patients after the first manifestation suggestive for a demyelinating disease (BENEFIT study), it was decided to organize a centralized eligibility assessment for this trial. During this eligibility assessment it was observed that there were marked inconsistencies in the decisions of participating neurologists with respect to the classification of clinical symptoms as being caused by one or more lesions provoking discussions in about one in every five patients. This paper describes these inconsistencies and their sources, and recommends a systematic approach that attempts to reduce the variability in interpreting clinical findings.
A preliminary report on a skills-based telephone-administered peer support programme for patients with multiple sclerosis
Authors: Mohr David C , Burke Heather , Beckner Victoria , Merluzzi Natalia
Published: March 2005

Objective: Peer-support interventions have shown no statistically significant or clinically meaningful effect on quality of life (QOL) or depressive symptoms for multiple sclerosis (MS) patients. Peer-support interventions for MS generally provide support but no skills training. The aim of this study was to evaluate a brief telephone-administered skills-training model of peer-support for patients with MS. Methods: Sixteen patients with MS showing signs of moderate distress received eight sessions of telephone-administered peer support (TAPS). TAPS is a manualized programme administered by peer-support counsellors diagnosed with MS. Using a workbook, peer-support counsellors teach skills to manage distress and MS symptoms. Subjective depression was assessed using the Center for Epidemiological Studies Depression Scale while objective depression was rated using the Hamilton Rating Scale for Depression. QOL was measured preand post-treatment using the SF-36. Results: The participants showed significant improvements on both the CESD (p=0.04) and the HRSD (p=0.01). Overall QOL improved significantly (p=0.045), however this was not reflected in either the Physical Health composite score or the Mental Health Composite Scale (p-0.17). Conclusions: These findings suggest that TAPS may prove to be an efficacious peer-support model for patients with MS.
Factors limiting maximal oxygen uptake in exertional monoparesis
Authors: White Lesley J , Dressendorfer Rudolph H
Published: March 2005

Strength and maximal oxygen uptake (VO2max) for each leg were compared in a trained multiple sclerosis (MS) patient with exertional left monoparesis. Left quadriceps strength and left leg VO2max were 22% and 30% lower, respectively, compared to the right (control) leg. Because the same O2 delivery system served each leg during exercise, VO2max of the paretic leg was not limited by cardiorespiratory factors but rather by strength and/or muscle oxidative capacity. However, training with monoparesis likely enhanced O2 extraction and aerobic work capacity of the right leg.
Spiroergometric and spirometric parameters in patients with multiple sclerosis: are there any links between these parameters and fatigue, depression, neurological impairment, disability, handicap and quality of life in multiple sclerosis?
Authors: Rasova K , Brandejsky P , Havrdova E , Zalisova M , Rexova P
Published: March 2005

One-hundred and twelve patients with multiple sclerosis were selected as population-based sample and examined on impairment (Expanded Disability Status Scale), disability (Barthel Index), handicap (Environment Status Scale), the quality of life (Multiple Sclerosis Quality of Life), fatigue (Modified Fatigue Impact Scale), depression (Beck Depression Inventory Score), respiratory function (spirometric parameters on spirometry) and physical fitness (spiroergometric parameters on a bicycle ergometer).

The aim of the study was to examine and analyse (descriptive statistics) spiroergometric and spirometric parameters in patients with multiple sclerosis. Firstly, we tested the hypothesis whether spiroergometric and spirometric parameters are decreased and whether there are any correlations between these parameters and measures of impairment, depression, disability, handicap and quality of life. Secondly, we tested the hypothesis whether there is any correlation between a possible deconditioning and fatigue, and between a possible respiratory dysfunction and fatigue in multiple sclerosis.

It results from this study that many spiroergometric parameters in patients with multiple sclerosis are significantly lowered in comparison to the population norm. A link can be found between some spiroergometric parameters and neurological impairment, disability, handicap and quality of life. It is not possible to prove any correlation between spiroergometric parameters and depression. From the spirometric parameters, these are expiratory flows that are significantly lowered in MS patients. It is not possible to prove any correlation between spirometric parameters and fatigue, depression, neurological impairment, duration of the disease, disability, handicap and quality of life in multiple sclerosis.
Insulin Resistance, the Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease
Authors: Angelico F. , Del Ben M. , Conti R. , Francioso S. , Feole K. , Fiorello S. , Cavallo M. G. , Zalunardo B. , Lirussi F. , Alessandri C. , Violi F.
Published: March 2005

Background/Aims: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion.

Methods and Results: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe.

In nondiabetic subjects, a progressive (P < 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome.

Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P < 0.01) compared with those with homeostasis model of insulin resistance below the median.

Conclusions: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.
Exercise Is Required for Visceral Fat Loss in Postmenopausal Women with Type 2 Diabetes
Authors: Giannopoulou I. , Ploutz-Snyder L. L. , Carhart R. , Weinstock R. S. , Fernhall B. , Goulopoulou S. , Kanaley J. A.
Published: March 2005

This study examined the effects of aerobic exercise without weight loss, a hypocaloric high monounsaturated fat diet, and diet plus exercise (D+E) on total abdominal and visceral fat loss in obese postmenopausal women with type 2 diabetes. Thirty-three postmenopausal women (body mass index, 34.6 ± 1.9 kg/m2) were assigned to one of three interventions: a hypocaloric high monounsaturated fat diet alone, exercise alone (EX), and D+E for 14 wk. Aerobic capacity, body composition, abdominal fat distribution (magnetic resonance imaging), glucose tolerance, and insulin sensitivity were measured pre- and postintervention. Body weight (∼4.5 kg) and percent body fat (∼5%) were decreased (P < 0.05) with the D and D+E intervention, whereas only percent body fat (∼2.3%) decreased with EX. Total abdominal fat and sc adipose tissue (SAT) were reduced with the D and D+E interventions (P < 0.05), whereas visceral adipose tissue (VAT) decreased with the D+E and EX intervention, but not with the D intervention. EX resulted in a reduction in total abdominal fat, VAT, and SAT (P < 0.05) despite the lack of weight loss. The reductions in total abdominal fat and SAT explained 32.7% and 9.7%, respectively, of the variability in the changes in fasting glucose levels, whereas the reductions in VAT explained 15.9% of the changes in fasting insulin levels (P < 0.05). In conclusion, modest weight loss, through either D or D+E, resulted in similar improvements in total abdominal fat, SAT, and glycemic status in postmenopausal women with type 2 diabetes; however, the addition of exercise to diet is necessary for VAT loss. These data demonstrate the importance of exercise in the treatment of women with type 2 diabetes.
Results of Long-Term Follow-Up after Treatment of Central Precocious Puberty with Leuprorelin Acetate: Evaluation of Effectiveness of Treatment and Recovery of Gonadal Function. The TAP-144-SR Japanese Study Group on Central Precocious Puberty
Authors: Tanaka Toshiaki , Niimi Hiroo , Matsuo Nobutake , Fujieda Kenji , Tachibana Katsuhiko , Ohyama Kenji , Satoh Mari , Kugu Koji
Published: March 2005

We evaluated the effect of leuprorelin treatment on adult height (AH) and followed recovery of reproductive function in 63 girls and 13 boys with central precocious puberty (CPP). Mean treatment durations were 3.8 ± 2.0 and 4.1 ± 2.5 yr, and posttreatment follow-up durations were 3.5 ± 1.3 and 2.6 ± 1.1 yr for girls and boys, respectively. AH was 154.5 ± 5.7 cm for girls, and 89.5% of girls reached AH within their target height range. For boys, AH was 163.2 ± 13.0 cm, and 90.9% reached target height range. It appeared that the Bayley-Pinneau method, modified for Japanese children, using a table for advanced bone age (BA), overestimated AH in CPP; and this method, using a table for average BA and projected height for BA, was suitable for prediction of AH in CPP.

Menarche or remenarche occurred in 96.8% of girls at the age of 13.1 ± 1.5 yr. Of 11 girls who contributed urine samples, all seven idiopathic and two organic cases were considered to have ovulation. Serum testosterone levels reached normal adult level in all boys.

In conclusion, long-term leuprorelin treatment for children with CPP improved AH and had no adverse effects on recovery of reproductive function.
Responses of Serum Androgen and Insulin Resistance to Metformin and Pioglitazone in Obese, Insulin-Resistant Women with Polycystic Ovary Syndrome
Authors: Ortega-González C. , Luna S. , Hernández L. , Crespo G. , Aguayo P. , Arteaga-Troncoso G. , Parra A.
Published: March 2005

Severe insulin resistance is a key abnormality in obese women with polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate whether pioglitazone decreases insulin resistance (IR) and hyperandrogenism to the same extent as metformin in obese women with PCOS who have not received any previous treatment. Fifty-two women with PCOS were randomly allocated to receive either pioglitazone (30 mg/d, n = 25) or metformin (850 mg three times daily, n = 27) and were assessed before and after 6 months. Body weight, body mass index, and waist to hip ratio increased significantly (P ≤ 0.05) after pioglitazone treatment but not after metformin treatment. Fasting serum insulin concentration (P < 0.001 for both drugs) and the area under the insulin curve during a 2-h oral glucose tolerance test decreased after pioglitazone (P < 0.002) or metformin (P < 0.05) treatment. IR (homeostasis model of assessment-IR index) decreased and insulin sensitivity (elevation of the quantitative insulin sensitivity check index and the fasting glucose to insulin ratio) increased (P ≤ 0.008) after treatment with either drug. Hirsutism (P < 0.05) and serum concentrations of free testosterone (P < 0.02) and androstenedione (P < 0.01) declined to a similar extent after treatment with the drugs. Treatment with pioglitazone or metformin was associated with the occurrence of pregnancy (n = 5 and n = 3, respectively). These results suggest that pioglitazone is as effective as metformin in improving insulin sensitivity and hyperandrogenism, despite an increase in body weight, body mass index, and the waist to hip ratio associated with pioglitazone.
Factors Associated with Celecoxib and Rofecoxib Utilization
Authors: Rawson Nigel SB , Nourjah Parivash , Grosser Stella C , Graham David J
Published: March 2005

BACKGROUND:

The cyclooxygenase-2 (COX-2) selective nonsteroidal antiinflammatory drugs (NSAIDs) celecoxib and rofecoxib (before its removal) are marketed as having fewer gastrointestinal (GI)-related complications than nonselective NSAIDs. However, adverse reaction data suggest that the use of COX-2 selective NSAIDs is associated with clinically significant GI events.

OBJECTIVE:

To assess whether patients receiving celecoxib and rofecoxib have a greater underlying disease burden than patients prescribed nonselective NSAIDs.

METHODS:

The study population consisted of members of 11 health plans, aged >34 years, with a pharmacy claim for celecoxib or rofecoxib or a nonselective NSAID dispensed between February 1, 1999, and July 31, 2001, who had been continuously enrolled for >364 days before the dispensing date. Celecoxib and rofecoxib patients were randomly selected without replacement from a pool of eligible users in each of the 30 months. Nonselective NSAID users were randomly chosen without replacement within each month on a 2:1 ratio to cases; they could be chosen in more than one month. Univariate analyses comparing 9000 cases and 18 000 controls were performed, followed by a multiple logistic regression analysis conditioned on time.

RESULTS:

Increasing age, treatment by a rheumatologist or an orthopedic specialist, treatment with a high number of different medications in the past year, treatment with oral corticosteroids in the past year, and having had a previous GI bleed increased the likelihood of receiving celecoxib or rofecoxib, whereas treatment with a high number of nonselective NSAID prescriptions in the past year decreased it. Treatment with a high number of different medications was a predictor of increased prevalence of underlying diabetes mellitus and cardiovascular disease.

CONCLUSIONS:

Patients having a greater underlying disease burden were more likely to receive COX-2 selective NSAIDs than nonselective ones. Paradoxically, patients at higher risk for cardiovascular disease were channeled toward treatment with COX-2 selective NSAIDs, many of which may confer an increased risk of acute myocardial infarction and other adverse cardiovascular outcomes.
Pharmacologic Treatment of Opioid-Induced Sedation in Chronic Pain
Authors: Reissig James E , Rybarczyk Amy M
Published: March 2005

OBJECTIVE:

To review the literature for pharmacologic management of opioid-induced sedation (OIS) in patients with chronic pain.

DATA SOURCES:

A search of MEDLINE (1966–October 2004) for English-language literature and selected bibliographies was completed. Search terms included pain, opioid, sedation, psychostimulants, amphetamines, modafinil, and donepezil.

DATA SYNTHESIS:

Amphetamines and amphetamine-like agents, caffeine, donepezil, and modafinil have been evaluated for OIS. Available literature is limited by numbers of subjects, duration, and trial design; however, there is limited support for the use of methylphenidate, donepezil, and modafinil.

CONCLUSIONS:

Pharmacologic treatment of OIS should be utilized selectively, given the available literature. Methylphenidate, donepezil, and modafinil may be considered in appropriate patients.
Staggered Transition to Epoprostenol from Treprostinil in Pulmonary Arterial Hypertension
Authors: Reisbig Katharine A , Coffman Pamela A , Floreani Anthony A , Bultsma Christopher J , Olsen Keith M
Published: March 2005

OBJECTIVE:

To describe a successful transition process from subcutaneous treprostinil to intravenous epoprostenol after the failure of treprostinil in a patient with idiopathic pulmonary arterial hypertension and present an algorithm to achieve the conversion without significant adverse reactions.

CASE SUMMARY:

A 25-year-old white female receiving subcutaneous treprostinil 97 ng/kg/min was admitted to the intensive care unit for transition from subcutaneous treprostinil to a target intravenous epoprostenol dose of 72 ng/kg/min via a staggered interval dose adjustment approach. The patient experienced facial flushing, hot flashes, and headache when dose adjustments of the drugs were made simultaneously; however, when dose adjustments were staggered, the adverse reactions did not occur and larger adjustments could be achieved.

DISCUSSION:

This case demonstrates a suboptimal therapeutic response to treprostinil for the treatment of idiopathic pulmonary arterial hypertension. The transition of treprostinil to epoprostenol is rare; however, in the event therapy change is needed, dosing information is minimal. A staggered transition dosing regimen that accounts for the pharmacokinetic differences between epoprostenol and treprostinil was successfully used in this case.

CONCLUSIONS:

The approach in this case demonstrates the success of staggered-interval dose adjustments to minimize supratherapeutic symptoms and coincides with the pharmacokinetic profile of the 2 medications.
Decreased Warfarin Effect after Initiation of High-Protein, Low-Carbohydrate Diets
Authors: Beatty Stuart J , Mehta Bella H , Rodis Jennifer L
Published: March 2005

OBJECTIVE:

To report 2 cases of decreased international normalized ratio (INR) after initiation of a high-protein, low-carbohydrate diet.

CASE SUMMARIES:

Case 1. A 67-year-old white woman had been receiving warfarin for 3 years for venous thromboembolism. After initiation of a high-protein, low-carbohydrate diet, the patient required a 22.2% increase (from 45 to 57.5 mg/wk) in warfarin dose. Her INR remained in the therapeutic range on this dose for 8 weeks. When the patient stopped the high-protein, low-carbohydrate diet, a decrease back to the original warfarin dose was required to return to a therapeutic INR. Case 2. A 58-year-old white man had been receiving warfarin for 8 years for a cerebrovascular accident. Initiation of a high-protein, low-carbohydrate diet resulted in a 30% increase (from 26.25 to 37.5 mg/wk) in warfarin dose. His warfarin dose was reduced to the original dose after he stopped the high-protein, low-carbohydrate diet.

DISCUSSION:

The Naranjo probability scale indicated a possible adverse effect between warfarin and high-protein diets. High-protein diets have been shown to increase serum albumin levels. This may result in more warfarin binding to serum albumin, thereby decreasing the anticoagulant effect of warfarin. The increase of albumin occurs rapidly after initiation of a high-protein diet and appears to promptly affect anticoagulation therapy with warfarin.

CONCLUSIONS:

These cases indicate a significant interaction between high-protein, low-carbohydrate diets and warfarin therapy. Patients receiving warfarin therapy should be educated on and monitored for the potential interaction that occurs with warfarin therapy and high-protein, low-carbohydrate diets.
Not by Discovery but by Conquest: The Use of History and the Meaning of ‘Justice’ in Australian Native Title Cases
Authors: Stuckey Michael
Published: March 2005

This article provides a critical assessment of Australian appellate courts' handling of historical evidence, at various levels and in various jurisdictions, over recent years in litigated Aboriginal land title disputes. Consideration is given to the courts' posture towards the evidence of historians, anthropologists and ethnographers, the extent to which such specialists have been considered ‘experts' or not, and the ways in which their evidence and accounts have been weighed and assessed. The article also examines the experience and contributions of the members of these professional groups who have been called to give evidence, and the challenges to their professional integrity that such appearances have sometimes involved. The paper concludes with an assessment of the extent to which the courts' interpretations of history in this important area of contemporary litigation have assisted or under***cut attempts to secure legal recognition of Aboriginal land rights.
Liability of Churches and Religious Organizations for Sexual Abuse of Children by Ministers of Religion
Authors: Meah Nafees , Petchey Philip
Published: March 2005

This paper considers the legal issues that arise in respect of the potential liability of churches and religious organizations for sexual abuse of children perpetrated by ministers of religion. This article analyses some of the leading recent US, Canadian and Australian appellate court decisions as well as the recent House of Lords decision in Lister v Hesley Hall. It is submitted that the way that other common law jurisdictions have approached the issue of sexual abuse of children will have an important influence on the way the English courts approach such cases in the future.
Attempting Fusion: Professor Worthington's ‘Equity’ and its Integration with the Common Law
Authors: Dietrich Joachim
Published: March 2005

Professor Sarah Worthington's new book, Equity seeks to achieve two related objects: first, ‘to expose Equity's impact on the modern legal landscape' and its ‘profound influence on the Common Law of property, contract, tort and unjust enrichment’; and, secondly, ‘to expose the possibilities for coherent substantive integration of the Common Law and Equity’. In short, the book attempts nothing less than to provide a simplified, rational and principled overview of the core concepts of Equity, its doctrines and remedies, in order to pursue the fusion of Equity and the Common Law. This article proposes to consider Worthington's book by outlining its burden, and then by engaging with some of the arguments made and conclusions drawn.
Protecting Bird Habitat of European Importance — The View from Basses Corbières
Authors: Machin Graham
Published: March 2005

This paper describes the operation of the habitat protection provisions of the EEC Birds Directive of 1979 in the light of changes made by the Habitats Directive of 1992, by reference to the case law of the European Court of Justice and especially the decisions of Commission v Spain (‘ Santoña Marshes’) in 1993 and Commission v France (‘ Basses Corbières’) in 2000. The effect of the Basses Corbières decision was first considered by a United Kingdom court in R (Bown) v Secretary of State for Transport, decided by Collins J at first instance on 26 March 2003 and by the Court of Appeal on 31 July 2003. The author reviews the relevant aspects of these two decisions, and concludes that, although the actual result in the case may well be correct, the Court of Appeal did not accurately identify and address the issues which it raised. The judgment of the Court of Appeal is inconsistent in important respects with the European cases, and therefore a potentially misleading authority for those, whether courts, ministers or inspectors, who have to make decisions about the status and protection of areas which, it is contended, should have been, but have not been, included by government in a classified special protection area under the Birds Directive.
Matching and Partially-Matching DNA Profiles
Authors: Weir BS
Published: March 2005

The DNA profiles of two individuals can have 0, 1, or 2 pairs of alleles that are the same at each locus. These events may be called mismatches, partial matches or matches, respectively, and they have probabilities that depend on the population proportions of alleles as well as the population structure parameter theta. The observed and expected numbers of pairs of individuals with various numbers of matching or partially matching loci in FBI and Australian databases are found to be in good agreement provided theta is set equal to some small value greater than zero. The likelihood ratios for two individuals having a specified degree of relationship versus being unrelated also depend on the numbers of matching and partially matching loci, but even unrelated pairs of individuals can have likelihood ratios that support hypotheses of relatedness. Matching probabilities allow predictions to be made for the sizes of databases that are expected to contain a pair of individuals with high numbers of matching loci. It is very likely that two individuals with at least 9 matching loci among the 13 CODIS loci have already been typed.
Mitochondrial DNA Heteroplasmy Among Hairs from Single Individuals
Authors: Sekiguchi K , Sato H , Kasai K
Published: March 2005

A denaturing gradient gel electrophoresis (DGGE) assay was used to detect mitochondrial DNA (mtDNA) sequence heteroplasmy in 160 hairs from each of three individuals. The HV1 and HV2 heteroplasmic positions were then identified by sequencing. In several hairs, the heteroplasmic position was not evident by sequencing and dHPLC separation of the homoduplex/heteroduplex species was carried out with subsequent reamplification and sequencing to identify the site. The overall detection frequency of sequence heteroplasmy in these hairs was 5.8% (28/480) with DGGE and 4.4% (21/280) with sequencing. Sequence heteroplasmy of hair was observed even when the reference blood sample of the individual was homoplasmic. The heteroplasmic positions were not necessarily observed at sites where high rates of substitution have been reported. In two hairs, a complete single base change from the reference blood sample was observed with sequencing, while the heteroplasmic condition at that site in the hair was observed using DGGE. The DGGE results in such samples would serve as an aid in considering the possibility of match significance. In a forensic case, this situation would lead to the possibility of a failure to exclude rather than to be inconclusive.
Postmortem Analysis of Anastomotic Suture Line Disruption Following Carotid Endarterectomy
Authors: Melinek J , Lento P , Moalli J
Published: March 2005

The tensile strength of a surgical suture is essential in maintaining the integrity of vascular anastomoses. While faulty operative technique and the loading strength of individual sutures have been implicated in spontaneous suture line disruptions, there has, to date, never been a published postmortem analysis of a suture that has known to have failed. We present the case of suture line disruption leading to fatal exsanguination in a 77-year-old man following carotid endarterectomy with a facial vein patch. Using both dissecting and scanning electron microscopy, we determined that surgical technique (an untied knot) was the cause of the suture line disruption. The removal of a broken or untied suture at surgery or at autopsy should not preclude proper analysis of the failed suture, because the results can have both medico-legal and public health implications.
Systematic Analysis of Stutter Percentages and Allele Peak Height and Peak Area Ratios at Heterozygous STR Loci for Forensic Casework and Database Samples
Authors: Leclair B , Fregeau CJ , Bowen KL , Fourney RM
Published: March 2005

To assist the interpretation of STR DNA typing results from forensic casework samples containing mixtures, the range of heterozygous allele peak height and peak area ratios (HR) and stutter percentages (stutter %) for the loci comprised in the AmpFℓSTR® Profiler Plus™ (PP) kit were assessed on 468 database and 275 casework single source samples. Stutter % medians were similar for database and casework samples, ranging from 2% to 7%. The upper limit of the stutter value range was 16%, calculated as median +3 SD, although lower locus-specific values could be used. HR medians were 93 ± 6.5% for database samples, 88 ± 12% for casework samples. For casework samples, the maximum signal imbalance noted was 52%, calculated as median -3 SD. No significant difference was observed between peak height and peak area calculated values. This study shows the importance of selecting the proper reference database for the establishment of HR threshold values.
Reconsidering the Auricular Surface as an Indicator of Age at Death
Authors: Osborne DL , Simmons TL , Nawrocki SP
Published: March 2005

Using standards established by Lovejoy et al. (l) to estimate age at death from auricular surface morphology, 266 individuals of documented age, sex, and ancestry from the Terry and Bass Donated Collections were scored. Analysis of covariance (ANCOVA) indicates that for the factors that could be controlled, age is the sole influence on auricular surface morphology. Ancestry and sex had no significant effect on auricular phase expression. No evidence of secular changes was detected when comparing the Terry Collection (early 20th century) to the Bass Collection (later 20th century). Pearson correlations reveal that several of the subcomponents of the auricular surface (superior and inferior demifaces, left and right sides, transverse organization, texture) correspond with age equally well, although a combined scoring of all features performs slightly better than any one indicator taken alone. Not surprisingly, only 33% of the sample was correctly aged when using the 5-year age ranges provided by Lovejoy et al. (l), suggesting that the published ranges are much too narrow to be used in forensic contexts. To assess the variation in age per phase, standard descriptive statistics and error ranges were calculated and can be employed by forensic anthropologists when estimating the age of an unidentified decedent. Because the mean ages of some of the eight phases did not differ significantly from one another, a modified six-phase system is presented. The auricular surface performs as well as any other single skeletal indicator of adultage. This research suggests that a statistically-informed approach should be taken in order to fully understand the drawbacks and limitations of any aging method.
Use of MDA (The "Love Drug") and Methamphetamine in Toronto by Unsuspecting Users of Ecstasy (MDMA)
Authors: Kalasinsky KS , Hugel J , Kish SJ
Published: March 2005

It has recently been reported that purity of illicit tablets of ecstasy (MDMA) is now high. Our objective was to confirm whether hair of drug users, who request only ecstasy from their supplier, contains MDMA in the absence of other drugs. GC-MS analysis of scalp hair segments disclosed the presence of MDMA in 19 of 21 subjects and amphetamine/methamphetamine in eight subjects. Surprisingly, seven subjects had hair levels of the MDMA metabolite, MDA, equal to or greater than those of MDMA, suggesting use of MDA in addition to that of MDMA. These amphetamine derivatives might be included by clandestine laboratories to enhance effects of the drug cocktail or because of a perception that MDA synthesis might be simpler than that of MDMA. Drug users and investigators examining possible brain neurotoxic effects of MDMA need to consider that “ecstasy” tablets can contain MDA and methamphetamine despite no demand for the drugs.
A Calibrated Gray Scale for Forensic Ultraviolet Photography
Authors: Dyer AG , Muir LL , Muntz WRA
Published: March 2005

The human eye is an important tool for observing evidence, and visual evidence in turn may be documented onto a photographic medium. The human eye is generally sensitive only to a narrow band of the electromagnetic spectrum from about 700 nm (red) to about 400 nm (violet/blue). It is possible to extend the range of radiations over which evidence may be documented by using the natural ultraviolet sensitivity of photographic films. However, photographing evidence with ultraviolet radiation ultimately involves presenting the information to subjects who may have no prior experience at viewing these wavelengths. This study shows that it is necessary to use a calibrated ultraviolet reflecting gray scale to allow meaningful interpretation of results.
Estimation of Caloric Deficit in a Fatal Case of Starvation Resulting from Child Neglect
Authors: Nagao M , Maeno Y , Koyama H , Seko-Nakamura Y , Monma-Ohtaki J , Iwasa M , Zhe LX , Kawashima N , Yano T
Published: March 2005

We report the case of a 3-year-20-day-old girl who died of starvation as a result of severe neglect. Her body weight had been 12 kg 70 days before her death, but was only 5 kg at the time of autopsy. From information supplied by her parents to police, we calculated her daily caloric intake and estimated the factors for physical activity. The daily recommended dietary allowance for the victim was calculated from 700 kcal/day × the appropriate factor for physical activity.

In the absence of enough food, body fat (7.2 kcal/g body fat) and protein (4 kcal/g protein) would have been used to compensate until death. The calculated body weight at the time of death was around 5 kg. The statements of the parents therefore appear to be true.
Tramadol (Ultram®) Concentrations in Death Investigation and Impaired Driving Cases and Their Significance
Authors: Clarkson JE , Lacy JM , Fligner CL , Thiersch N , Howard J , Harruff RC , Logan BK
Published: March 2005

We reviewed a series of 66 deaths in Washington State between 1995–2000 in which tramadol (Ultram® and Ultracet®, Ortho-McNeil) was detected in the decedent's blood, in order to assess the role tramadol was determined to have played. Additionally, we reviewed a series of 83 impaired driving cases in which tramadol was detected in order to establish a non-lethal blood tramadol concentration reference range. In both populations, tramadol was consistently found together with other analgesic, muscle relaxant, and CNS depressant drugs. Death was rarely attributable to tramadol alone. However, tramadol may be a significant contributor to lethal intoxication when taken in excess with other drugs, via the potential interaction with serotonergic antidepressant medications, as well as the potential for increased CNS depression. Although the incidence of tramadol detection has increased consistently over the last eight years, there is no evidence of a corresponding increase in the number of cases in which death was attributed solely to tramadol. Blood drug concentrations in many deaths exceeded the therapeutic serum range of 0.28–0.61 mg/L (1); however, the concentrations overlapped almost completely with the range identified in living subjects arrested for impaired driving. These findings suggest caution in the interpretation of blood tramadol concentrations outside of the recognized therapeutic range. It also suggests that the drug, even when used in moderate excess, is not a principle cause of death in suicidal or accidental deaths.