A benefit/risk assessment of existing therapeutic alternatives for the treatment of painful inflammatory conditions.

Pain remains the leading reason for which patients consult their doctors. Pain also motivates over-the-counter sales of analgesic medicines, to be taken orally or even transcutaneously. Prescription medicines usually follow attempts at self-medication that fail to achieve the desired results. Acute pain usually subsides spontaneously but medicines are needed until that occurs; in arthritic conditions--especially osteoarthritis--anti-inflammatory drugs work best in short-term administration for flares that aggravate chronic but tolerable pain. In cases of chronic pain that exceeds the level of easy tolerance, anti-inflammatory drugs can reduce the pain to tolerable levels more effectively than simple analgesics and narcotic combinations. The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most useful medicines providing an array of drugs that differ chiefly in time of onset of action, duration of action and persistence in the blood. The benefit they provide is pain amelioration; none is curative. The risks are well known and do not differ greatly among the drugs; unwanted gastrointestinal (GI) effects are the most common, but the skin, kidneys, liver and blood forming organs may also be affected. As the benefits are similar, when balancing risk and benefit it is important to: consider the cause and expected duration of pain, balance the risks (GI unwanted effects far outnumber others), assess the severity and likelihood of specific reactions, and consider the costs--not only of the medicines themselves but also those of treating untoward reactions. Thus NSAIDs number among the most successful therapeutic options of modern medicine and, as pain will continue to require intervention, will likely continue--at least as ancillary medications--even as more definitive treatments are developed. In addition, the target population, its characteristics and the duration and acceptance of the intervention need to be considered.

Back pain.

Back pain is ubiquitous and probably plagues almost everyone in all cultures and ethnic groups at some time (around 20% annually), and in up to 50% of these at least once a year. The WHO-COPCORD epidemiologic investigations have established its prevalence even in countries that had been unaware of its frequency in their populace, and factors involving type of work and training probably accounted for this misperception. Medical journals are replete with articles addressing diagnosis and treatment, but the majority fail to meet the standards needed for metaanalysis or comparison. A task force of the Agency for Health Care Policy and Research of the United States Department of Health and Human Services screened more than 10,000 abstracts, eliminated the majority of these studies and papers, and still was unable to recommend the best approach even to acute back pain; the problem of subacute and chronic back pain is even more formidable. Yet back pain has been identified as perhaps the major cause of disability and absenteeism from the workplace worldwide. WHO chiefly addressed subacute back pain, as most acute back pain is self-limited and ends spontaneously, almost regardless of the treatment. Subacute pain is the intermediate stage toward chronic pain, which defies most treatments. Specific causes for back pain, such as infections, tumors, osteoporosis, spondyloarthropathies, and trauma, actually represent a minority of such pain syndromes, qualifying for specific therapeutic approaches. A major problem in defining the burden of disease for back pain has been a dearth of agreed-upon outcome measures by which to judge the various interventions, and this was the task that the WHO Low Back Pain Initiative took upon itself. Among measures recommended to be included in all studies, so that valid comparisons could be made, were measurement of pain by visual analog scales, somatic perception, the Oswestry disability and modified Zung questionnaires, and a modified Schober test of spinal mobility. These measures are needed for studies, not for diagnosis or treatment of individual patients. They have been translated into various major languages and validated by back-translations, and applied in comparative studies in various cultures to medical, chiropractic, and other common interventions. The importance of such scientifically sound studies cannot be overemphasized, as the costs of health care are mounting everywhere and it therefore becomes imperative to develop cost-effective approaches. All the more so as conversion of acute back pain to chronic back pain is often iatrogenic, with strong psychosocial factors as well, so that not only what to do but also what not to do become important public health issues. The general lack of attention to back pain by governments and organizations probably results from the fact that it is perceived as a syndromic presentation with myriad causes rather than as a specific disease entity. Even if the "disease" names classify like presentations but are not necessarily etiologically discrete, syndromic diagnoses that subsume a variety of causes receive less attention; international rankings of common disabilities and public health problems tend to emphasize the named disorders rather than the grouped disorders. Moreover, back pain is often self-treated with nonprescription medications or alternative therapies, and by nonmedical practitioners or treatments in many parts of the world. Validation of outcomes therefore not only reduces invalidism and direct costs but also reduces the indirect costs of absenteeism and medical care.

Inhaled corticosteroids effects on bone in asthmatic and COPD patients: a quantitative systematic review.

Deleterious effect of oral corticosteroids on bone has been well documented, whereas this remains debated for inhaled ones (ICS). Our objectives were to analyze the effects of ICS on bone mineral density, fracture risk and bone markers. We performed an exhaustive systematic research of all controlled trials potentially containing pertinent data, peer-reviewed by a dedicated WHO expert group, and comprehensive meta-analyses of the data. Inclusion criteria were ICS, and BMD/markers/fractures in asthma/chronic obstructive pulmonary diseases (COPD) and healthy patients. Analyses were performed in a conservative fashion using professional dedicated softwares and stratified by outcome, study design and ICS type. Results were expressed as standardized mean difference/effect size (ES), relative risk (RR) or odds ratio (OR), depending on study design and outcome units. Publication bias was investigated. Twenty-three trials were reviewed; 11 papers fit the inclusion criteria and were assessed for the main analysis. Quality scores for the randomized controlled trials (RCTs) were 80%, 71% for the prospective cohort studies, and 78% for the retrospective cohort and cross-sectional studies. We globally assessed ICS effects on BMD and found deleterious effects: ES=0.61 ( p=0.001) for healthy subjects, and ES=0.27 ( p<0.001) for asthma/COPD patients. For these patients, this effect was 0.21 ( p<0.01) at the lumbar spine, and 0.26 ( p<0.001) at the hip or femoral neck. A single study evaluated the impact of ICS on hip fracture and reported an increased OR of 1.6 (1.24; 2.03). Lumbar fracture rate differences did not reach the level of statistical significance: 1.87 (0.5; 6.94). Osteocalcin and PICP were decreased and ICTP, pyridinoline and deoxypyridinoline levels were not significantly affected. Budesonide (BUD) appeared to be the ICS inducing the less deleterious effects on bone, followed by beclomethasone dipropionate (BDP) and triamcinolone (TRI). Publication bias investigation provided non-significant results. In our meta-analyses, BUD at a mean daily dose (SD) of 686 microg (158 microg), BDP at 703 microg (123 microg) and TRI at 1,000 microg (282 microg) were found to affect bone mineral density and markers in patients suffering from the two major respiratory diseases. These findings could have practical implication in the long-term management of asthmatic and COPD patients.

Low back pain.

Low back pain is a leading cause of disability. It occurs in similar proportions in all cultures, interferes with quality of life and work performance, and is the most common reason for medical consultations. Few cases of back pain are due to specific causes; most cases are non-specific. Acute back pain is the most common presentation and is usually self-limiting, lasting less than three months regardless of treatment. Chronic back pain is a more difficult problem, which often has strong psychological overlay: work dissatisfaction, boredom, and a generous compensation system contribute to it. Among the diagnoses offered for chronic pain is fibromyalgia, an urban condition (the diagnosis is not made in rural settings) that does not differ materially from other instances of widespread chronic pain. Although disc protrusions detected on X-ray are often blamed, they rarely are responsible for the pain, and surgery is seldom successful at alleviating it. No single treatment is superior to others; patients prefer manipulative therapy, but studies have not demonstrated that it has any superiority over others. A WHO Advisory Panel has defined common outcome measures to be used to judge the efficacy of treatments for studies.