The third issue of volume two of Therapeutics and Clinical Risk Management presents
review articles and original research papers on a wide range of topics.
World Health Organisation guidelines indicate morphine use for control of moderate-to-severe
pain in chronic cancer based on factors such as accessibility, effectiveness, ease
of administration, and cost as opposed to its being therapeutically superior. Survey
data from the Research Network of the European Association for Palliative Care indicate
that opioid rotation may achieve more effective pain control with fewer side effects
than single usage alone. Oxycodone is a member of the opioid class with high oral-to-parenteral
bioavailability with no threshold in its analgesic effect. Giuseppe Biancofiore examines
the pharmacokinetics and pharmacodynamics of oxycodone and reviews a selection of
studies examining its efficacy and safety profile in the treatment of cancer pain.
Considerable evidence exists to support the use of the bisphosphonate alendronate
sodium in the management of osteoporosis. Prinsloo and Hosking comprehensively discuss
the fracture intervention trial (FIT), a major grouping of four pivotal studies that
demonstrated alendronate's efficacy and provided the foundation for subsequent clinical
trials and a range of post-hoc analyses. The two studies of the vertebral fracture
arm, the clinical fracture arm and the osteoporotic cohort are all critically evaluated
in depth and the results expanded upon in the discussion of the prevention of multiple
fractures, prediction of responses to treatment, and aspects of primary prevention.
In addition, the authors present data relating to the role of alendronate in the management
of male osteoporosis and in corticosteroid-induced osteoporosis.
Mucositis-related pain is one of the primary side effects of cancer treatment with
approximately 40% of chemotherapy patients and most patients undergoing bone marrow
transplant affected. Despite the plethora of current therapies, none is especially
specific to or effective in mucositis. Debra Harris reviews recent advances in our
knowledge of pain management in mucositis including its pathophysiology, clinical
manifestations and the strengths and weaknesses of the respective assessment tools
including the Harris mucositis-related pain assessment tool that is specific to mucosal
pain and contains dimensions of pain; functional ability; and effectiveness of interventions.
Although the tool is as yet unvalidated it contains numerous validated elements from
other assessment methods. The author concludes with a range of key recommendations
aimed at standardising assessment, classification and patient treatment in a mucositis-specific
manner.
Cervical cancer is the second most common malignancy amongst females worldwide. In
their overview Winters et al examine the role of vaccination against human papilloma
virus by highlighting a range of recent studies considered to be of greatest relevance
to cervical cancer. Their approach includes discussion of pathology, epidemiology
and current prevention strategies and treatment. Furthermore the authors examine studies
of vaccines in development, prophylactic vaccines and some relevant associated contentious
issues.
Bortezomib is a novel proteasome inhibitor whose introduction heralds a major advance
in the management of multiple myeloma and as first-line therapy prior to stem cell
transplantation. Bortezomib is notable for its positive response in the previously
refractory patient and enhanced survival rates in the relapsed patient, data that
led to its approval by regulators in the US in 2003 and in Europe in 2005. In this
review, Antonia Field-Smith and colleagues present a comprehensive overview of findings
from Phase II/Phase III clinical trials and address its clinical use, including side
effects and toxicity; management of associated peripheral neuropathy (which affects
30% to 40% of patients) and thrombocytopenia. Finally, the authors give a comprehensive
overview of bortezomib in combination with other chemotherapeutic agents and conclude
that it is effective when administered in the outpatient setting.
A range of management strategies exists which can attenuate the sequelae of age-related
osteoporosis. MacLaughlin et al review the background to the topic and discuss epidemiology
and economic impact, diagnosis and classification together with an analysis of the
intrinsic and extrinsic risk factors for fall-related fractures. In addition, they
provide information on the respective roles of many pharmacological therapies including:
calcium and vitamin D; the bisphosphonates; calcitonin; estrogen receptor stimulators;
strontium ranelate; sodium fluoride; and teriparatide.
Secondary hyperparathyroidism (SHPT) is a serious clinical outcome of chronic renal
disease. The renal impairment-associated decline in active vitamin D (calcitriol)
is critically linked to the development of SHPT and its allied cardiovascular complications.
While intravenous vitamin D analogues such as paricalcitol are routinely used in hemodialysis
patients, the US FDA approved a novel oral paricalcitol preparation for use in prechronic
kidney disease in 2005. Cheng and Coyne review the data underpinning oral paricalcitrol
and consider its potential long-term benefits for reduced hospitalizations and enhanced
survival and include a brief discussion of its emerging role in the attenuation of
vascular calcification, atherosclerosis and renal fibrosis.
Migraine is a prevalent condition predominantly affecting females with approximately
half of these being susceptible to menstrual headache onset. This may last longer
and demonstrate greater resistance to treatment than other forms of migraine. Frovatriptan,
a 5-HT receptor agonist, is a second-generation triptan with a pharmacokinetic profile
of proven benefit in the management of menstrual migraine. Ebrahim Balbisi reviews
its pharmacology and pharmacokinetics and discusses the clinical efficacy, safety
and tolerability of frovatriptan in the treatment of this common and distressing condition.
Non-standard prescribing practices have been found to play a significant role in the
under-utilisation of anticoagulant drugs. The technique of academic detailing aims
to enhance prescribing behavior and has been used successfully in both community and
hospital environments. Roberts and Adams examined the effects of introducing guidelines
based on academic detailing on initiation of warfarin therapy, reversal of warfarin
over anticoagulation, and uptake of deep vein thrombosis phrophylaxis in four teaching
hospitals. The authors report that use of academic detailing enhanced guideline roll-out,
produced positive results in the majority of areas studied and was well-received by
prescribing practitioners.
Small-cell lung cancer (SCLC) has a poor prognosis associated with significant morbidity,
mortality and economic cost. Although several novel, third-generation chemotherapeutic
drugs are available for SCLC treatment, their cost effectiveness have yet to be fully
determined. Uylde Groot and colleagues have developed a Markov chain model for the
projection of patient outcome parameters and associated costs in SCLC for patients
treated with either etoposide–cisplatin combination therapy or a hypothetical new
drug. They conclude that increased future costs for SCLC treatment will result in
only a relatively minor extension of survival time. However, both palliation and quality
of life parameters should also be enhanced and the authors predict enhanced outcome
and cost-effectiveness with emerging treatment regimens.
Psoriasis therapy represents a substantial healthcare expenditure that was previously
estimated at $1.6bn–3.2bn in the US alone; the recent emergence of 3 novel biologic
response modifiers has significantly increased this projection. Cost-utility analysis
(CUA) utilises quality-adjusted life years (QALYs) as an effectiveness endpoint and
between US$50–100 000 is considered an affordable therapeutic intervention. Weiss
et al used Euro-Qol 5 Dimension (EQ5D), an instrument that has been standardized for
the description and evaluation of health states, in order to formulate a preliminary
CUA of psoriasis therapy. The authors conclude that current psoriasis therapeutics
confer comparable utilities relative to those in other medical specialties.
Gastroesophageal reflux disease (GERD) is a highly prevalent, unpleasant and debilitating
condition characterized by heartburn and regurgitation of food, the latter being association
with Barrett's esophagus and adenocarcinoma of the esophagus and gastric cardia. Nowak
and colleagues conducted a retrospective case series study of 23 adult patients who
attended a dietetic clinic for lifestyle intervention in the management of GERD. The
authors report that 22 patients reported an improvement in their symptoms and noted
a reduction in medication usage amongst 11 of the 18 patients who had been taking
GERD medication at time of presentation. In spite of the small number of patients
studied, their results indicate further evaluation of the role of lifestyle modification
in GERD is warranted.