A systematic review of treatments for the painful heel.

OBJECTIVE: To establish the efficacy for treatments of pain on the plantar aspect of the heel. METHODS: Systematic review of the published and unpublished literature. Electronic search of Medline, BIDS and the Cochrane database of clinical trials. An assessment of the quality of the reporting was made of studies included in the review. Main outcome measure: patients' pain scores. Study selection: randomized controlled trials, published or unpublished, that evaluated treatments used for plantar heel pain. Foreign language papers were excluded. RESULTS: Eleven randomized controlled trials were included in the review. These evaluated some of the most frequently described treatments (steroid injections and orthoses) and some experimental therapies (extracorporeal shock wave therapy and directed electrons). The methodological assessment scores of the published trials were low; small sample sizes and failure to conceal the treatment allocation from study participants prevents more definitive statements about the efficacy of treatments. In 10 of the included trials, patients in both the intervention and control arms reported improved pain scores at the final outcome measure. CONCLUSIONS: Although much has been written about the treatment of plantar heel pain, the few randomized controlled trials involve small populations of patients and do not provide robust scientific evidence of treatment efficacy.     

WHO‐ILAR‐COPCORD in the Asia‐Pacific: the past,present and future

The aim of the Community Oriented Program for Control of Rheumatic Disorders (COPCORD) is reduction of community burden of rheumatic disorders, particularly in developing communities. Stage I entails estimation of prevalence and incidence of musculoskeletal pain and rheumatic disorders. Stage II is dedicated to education of health workers, patients and the community. Stage III deals with identification of risk factors for common rheumatic disorders and development of strategies for their primary and secondary prevention. So far Stage I data have been reported from 15 countries in the Asia‐Pacific countries. The prevalence of musculoskeletal pain has varied from 11.6% to 45.4%. The commonest sites of pain were low back, knee, neck and shoulder. Commonest rheumatic disorders were osteoarthritis of knees, non‐specific low back pain and soft tissue rheumatism. A few scattered educational activities have been reported from Indonesia and India. Systematic case‐controlled or cohort studies aimed at finding out the risk factors for common rheumatic disorders were scanty. However, several associations were reported from cross‐sectional prevalence surveys. It is imperative that the COPCORD investigators in the Asia‐Pacific region focus on finding out the modifiable risk factors for rheumatic disorders with properly designed studies, develop preventive strategies on the basis of identified risk factors and carry out interventional studies to test the efficacy of the strategies with validated outcome instruments.     

Treatment of reflex sympathetic dystrophy with pamidronate: 29 cases.

OBJECTIVE: To evaluate the efficacy of treatment with pamidronate in reflex sympathetic dystrophy (RSD) refractory to previous treatment. METHODS: We studied the response (disappearance of pain and functional improvement) to pamidronate (60 mg/day for 3 days) in 29 patients with RSD refractory to previous treatment for at least 14 days. RESULTS: On day 45, complete pain disappearance was observed in 86.2% of patients and functional improvement in 70%. The mean delay until the pain disappeared was 20+/-14 days and the delay until functional improvement was observed was 29+/-18 days. The mean delay of functional improvement was shorter in patients with post-traumatic RSD. Multivariate analysis did not reveal any factor predictive of response to treatment. Six (20.7%) patients suffered from side-effects (fever, diarrhoea). CONCLUSION: Pamidronate appeared to be effective in the treatment of refractory RSD; however, these results need to be confirmed by a controlled placebo study.     

Maternal and infant outcome after pamidronate treatment of polyostotic fibrous dysplasia and osteogenesis imperfecta before conception: a report of four cases

BACKGROUND: Pamidronate is used extensively for treatment of osteoporotic and high bone turnover conditions. Because it has a long retention time in the human skeleton, concerns have been raised as to safety profile in women of child-bearing age. METHODS: Four infant outcomes of pregnancies of three women, two with polyostotic fibrous dysplasia and one with osteogenesis imperfecta, all of whom were treated with iv pamidronate before conception, are reported, with biochemical, radiological, and bone density data. RESULTS: Each pregnancy was uncomplicated, and the four offspring are healthy, with no evidence of biochemical or skeletal abnormality. CONCLUSIONS: We found no evidence for adverse effects of prepregnancy pamidronate on maternal or fetal health. Until the results of systematic studies are available, caution is recommended regarding pamidronate use in women of child-bearing years.     

Agents anti-TNFα et sarcoïdose

Increased production of TNFα by alveolar macrophages and involvement of TNFα in granuloma formation suggest that this cytokine is involved in the pathophysiology of sarcoidosis. The three available TNFα blocking agents have been tested in sarcoidosis refractory to corticosteroids or immunosuppressive drugs. Data are available from isolated case reports or limited series of patients treated in open label trials with favourable issue with anti-TNFα monoclonal antibodies. Two randomized placebo controlled studies evaluated the efficacy of infliximab in pulmonary and extra-pulmonary sarcoidosis, showing that infliximab improves significantly extra-pulmonary disease. There is no significant difference between infliximab and placebo in the treatment of pulmonary manifestations. Etanercept showed no efficacy for treating ocular sarcoidosis in a controlled trial and for pulmonary disease in an open label trial. Paradoxical cases of proven sarcoidosis have been reported in patients receiving anti-TNFα agents for chronic inflammatory rheumatic diseases. A literature review identified 28 cases, including 16 with etanercept, eight with infliximab and four with adalimumab. Although these cases were mainly reported with etanercept, paradoxical sarcoidosis has been reported with the three available anti-TNFα agents, suggesting a class effect. Changes in the cytokine balance may be involved in these cases of induced sarcoidosis, which must be known by the clinician.     

Phyto-anti-inflammatories. A systematic review of randomized, placebo-controlled, double-blind trials

Herbal treatments are often used to treat rheumatic symptoms. This systematic review is aimed at determining the clinical efficacy of this approach. Computer literature searches are carried out to locate all placebo-controlled, double-blind, randomized trials in this area. Nineteen studies meet the inclusion criteria. They are heterogeneous in terms of remedies tested, patients treated, and trial methodology applied. Most of the studies suggest that herbal remedies can have symptomatic effects beyond placebo. It is concluded that phyto-anti-inflammatories have considerable, albeit under-researched, potential in the symptomatic treatment of rheumatic disorders.     

Recent advances in the treatment of the spondyloarthropathies

PURPOSE OF REVIEW: Recently, there has been renewed interest in the spondyloarthropathy family of chronic inflammatory rheumatic conditions, which has been fueled to a large extent by the biologic era. Over the period of the past 2 years in particular, there have been several notable advances. First, there have been a number of large, high-quality randomized controlled trials evaluating the tumor necrosis factor (TNF) blockers and conservative treatments such as physiotherapy and nonsteroidal anti-inflammatory drugs for use in spondyloarthropathy. This has paved the way for the development of better tools to assess outcome in these patients both in daily practice and in the context of clinical trials. This review uses a systematic approach to outline the most recent (within the last 2 years) and the most pertinent advances in the treatments of the spondyloarthropathies, with particular emphasis on ankylosing spondylitis and psoriatic arthritis. RECENT FINDINGS: Supervised group exercise programs maintain flexibility and posture in patients with ankylosing spondylitis, and spa therapy is a cost-effective treatment option in ankylosing spondylitis. Nonsteroidal anti-inflammatory drugs have a role in symptom modification and, more importantly, may prevent structural disease progression in patients with ankylosing spondylitis when administered continuously at a fixed dose. TNF blockers have been evaluated in a number of randomized controlled trials in ankylosing spondylitis and psoriatic arthritis and have been demonstrated to be safe and effective in the short-term management of these diseases. Longer-term trials are awaited with radiographic outcomes to comment on their disease-modifying properties and their long-term safety and efficacy profiles. SUMMARY: There has been renewed interest in the spondyloarthropathy family of disorders, with an explosion in the number of trials evaluating outcome with the TNF blockers. To date, no cure has been found for the disease, but these agents are emerging as the best therapeutic option available for patients with ankylosing spondylitis and psoriatic arthritis to date.     

The evidence for acupuncture as a treatment for rheumatologic conditions

Individuals with rheumatic disorders, particularly those with more severe, chronic conditions, are likely to be frequent users of complementary and alternative medical therapies. Although large-scale clinical trials have yet to be conducted, there is moderately strong evidence that acupuncture may be effective for treating both osteoarthritis and fibromyalgia. The utility of acupuncture in treating rheumatoid arthritis has not been demonstrated in large, randomized controlled trials. Physicians who treat patients with rheumatic conditions should become knowledgeable about the literature on both the effectiveness of acupuncture for these conditions as well as its potential to cause adverse side effects in particular patient groups.     

Pharmacological therapies in fibromyalgia

The fibromyalgia syndrome (FMS) is a common, chronic, widespread pain disorder that mainly affects middle-aged women. In addition to pain complaints, fatigue and disturbed sleep are symptoms frequently reported by these patients. Many FMS patients also meet diagnostic criteria for mood disorders (e.g. depression) as well as other so-called 'functional somatic syndromes', including irritable bowel syndrome, temporomandibular joint disorder, and subsets of chronic low-back pain. A wide variety of medications are used to manage the eclectic symptomatology of FMS patients, although relatively few have been rigorously tested. This chapter provides a contemporary update of the state of FMS pharmacotherapy, with an emphasis on compounds that have been tested in double-blind, randomized, controlled trials. Particular attention is paid to the efficacy of these therapies on the associated symptoms and co-morbid syndromes commonly seen in FMS patients.     

Urethral Sphincter Injection of Botulinum Toxin A: A Review of Its Application and Outcomes

The first reported application of Botulinum toxin‐A (BTX‐A) into the urethral sphincter predates the first documented use in the bladder. The aim of this review is to describe the clinical indications of BTX‐A injection into the urethral sphincter and its clinical efficacy. This review of the literature includes the larger more significant published studies that have reported on this use of BTX‐A. Case reports and articles not published in English were excluded. There have been many published clinical studies describing the use of BTX‐A in the urethral sphincter, four of which are randomized placebo controlled trials. These studies tend to include patients either in urinary retention or with obstructed voiding, both in the neuropathic and non‐neuropathic populations. Studies tend to demonstrate improvements in urodynamic parameters and quality of life after injection. There have been many small clinical studies in this area, however larger placebo‐controlled trials are needed to evaluate this treatment at higher levels of evidence.     

The use of pamidronate in hypertrophic pulmonary osteoarthropathy (HPOA)

Background: Hypertrophic pulmonary osteoarthropathy (HPOA) secondary to bronchogenic carcinoma can be associated with severe, disabling pain which is not always responsive to conventional treatment.
Aim: To report on the use of pamidronate to control resistant pain in HPOA in three cases.
Methods: A retrospective review of reported pain, chest X-ray and radionuclide bone scans was made.
Results: Pain relief was achieved in all three cases together with reduced radiolabel uptake in two cases.
Conclusions: Pamidronate appears to be an effective therapy for HPOA. Further investigation is warranted.     

Pamidronate in the treatment of childhood SAPHO syndrome

BACKGROUND: SAPHO syndrome is increasingly recognized within the paediatric population. Conventional therapeutic approaches have often not been effective. Pamidronate is a second-generation bisphosphonate that affects bone turnover and demonstrates anti-inflammatory properties. In small case series it has given symptomatic relief to adults with this condition. OBJECTIVES: To report the clinical experience with pamidronate in childhood SAPHO syndrome. METHODS: A retrospective observational study of all children with SAPHO syndrome treated with pamidronate between 1996 and 2003 at a tertiary rheumatology centre. The standard dosing regime for pamidronate was 1 mg/kg to a maximum of 30 mg, administered daily for three consecutive days, repeated 3-monthly as required. Response to treatment was determined by clinical observation, patient subjective response and reduction in other treatments RESULTS: Seven girls were treated, with a median (range) age at diagnosis of 11 yr (9-15 yr). All patients demonstrated a beneficial clinical response, with relief of pain, increased activity and improved well-being. Subsequent courses of pamidronate were used in all patients. Other medications including corticosteroids and methotrexate could subsequently be stopped. Transient symptoms were associated with the initial course of pamidronate in some patients. No serious adverse events were reported. CONCLUSIONS: Pamidronate was associated with a marked improvement in function and well-being, and a reduction of pain and use of other medications in all patients, with no significant adverse effects. This study represents preliminary clinical data. A prospective multicentre study is necessary to assess the role and long-term safety of pamidronate in the management of childhood SAPHO syndrome     

Antioxidant vitamins in the prevention of cardiovascular disease: a systematic review

Abstract. Asplund K (Umeå and Stockholm, Sweden). Antioxidant vitamins in the prevention of cardiovascular disease: a systematic review (Review). J Intern Med 2002; 251: 372–392. Do antioxidant vitamins, in regular food or as food supplements, protect against myocardial infarction and stroke? In this systematic literature review on the effects of antioxidant vitamins in the primary prevention of cardiovascular disorders, studies with ischaemic heart disease, stroke or combined cardiovascular events as end‐points have been included. Studies on the effects of antioxidant vitamins on intermediary end‐points (such as blood lipids and blood pressure) and as secondary prevention in patients with manifest cardiovascular disease are reviewed in a conventional manner. In observational studies (case–control or cohort design), people with high intake of antioxidant vitamins by regular diet or as food supplements generally have a lower risk of myocardial infarction and stroke than people who are low‐consumers of antioxidant vitamins. The associations in observation studies have been shown for carotene, ascorbic acid as well as tocopherol. In randomized controlled trials, however, antioxidant vitamins as food supplements have no beneficial effects in the primary prevention of myocardial infarction and stroke. Serious adverse events have been reported. After an initial enthusiasm for antioxidants in the secondary prevention of cardiovascular disease, recent reports from of several large randomized trials have failed to show any beneficial effects. Thus, the apparent beneficial results of high intake of antioxidant vitamins reported in observational studies have not been confirmed in large randomized trials. The discrepancy between different types of studies is probably explained by the fact that supplement use is a component in a cluster of healthy behaviour. Antioxidant vitamins as food supplements cannot be recommended in the primary or secondary prevention against cardiovascular disease.     

Diabetes mellitus and metformin in hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the leading cause of cancer-related death worldwide. Diabetes mellitus, a risk factor for cancer, is also globally endemic. The clinical link between these two diseases has been the subject of investigation for a century, and diabetes mellitus has been established as a risk factor for HCC. Accordingly, metformin, a first-line oral anti-diabetic, was first proposed as a candidate anti-cancer agent in 2005 in a cohort study in Scotland. Several subsequent large cohort studies and randomized controlled trials have not demonstrated significant efficacy for metformin in suppressing HCC incidence and mortality in diabetic patients; however, two recent randomized controlled trials have reported positive data for the tumor-preventive potential of metformin in non-diabetic subjects. The search for biological links between cancer and diabetes has revealed intracellular pathways that are shared by cancer and diabetes. The signal transduction mechanisms by which metformin suppresses carcinogenesis in cell lines or xenograft tissues and improves chemoresistance in cancer stem cells have also been elucidated. This review addresses the clinical and biological links between HCC and diabetes mellitus and the anti-cancer activity of metformin in clinical studies and basic experiments.     

Randomized trials in the treatment of Barrett''s esophagus

Treatment for Barrett's esophagus (BE) has consisted of medical treatment (acid suppression medications), surgery (fundoplication) and endoscopic ablative techniques (photodynamic therapy, argon plasma coagulation and multipolar electrocoagulation). Despite the large number of clinical trials of the efficacy of different therapeutic modalities, there is a paucity of published randomized controlled trials. The aim of this review is to evaluate the published randomized therapeutic trials in patients with BE. A comprehensive MEDLINE search was performed to review randomized clinical trials of different therapeutic modalities in BE. Only eight randomized studies have been published. The eight randomized studies reviewed include: two trials that evaluated medical and surgical therapy; two placebo controlled trials for photodynamic therapy (PDT); one placebo controlled trial comparing argon plasma coagulation (APC) versus surveillance; two trials comparing PDT versus APC; and one trial comparing APC versus multipolar electrocoagulation (MPEC). All the studies are prospective, however only one study is double-blinded. Each study has a small sample size, uses a different population of BE patients (dysplasia versus no dysplasia, short segment BE versus long segment BE), has different defined endpoints (endoscopic ablation of BE, number of treatments required for endoscopic ablation of BE, and elimination of high grade dysplasia) and the methodology for the treatment modalities is different among the studies. Though the data to support the use of endoscopic ablative techniques in the treatment of BE are promising, more rigorous double-blind and larger, well designed randomized studies are required to draw any definitive conclusions.     

New therapies for the rheumatic diseases

The investigational therapies of the rheumatic diseases reviewed in this issue are at various stages of clinical development. Methotrexate and sulfasalazine represent examples of chemotherapies in which the short-term efficacy and toxicities, at least in rheumatoid arthritis, have been carefully documented by controlled trials. The limited information available on cyclosporin A, combination chemotherapy, and radiotherapy is encouraging and appears to warrant additional, more extensive studies. In particular, randomized trials to determine the effects of these interventions on relevant long-term outcomes such as functional disability, organ failure, and life expectancy are necessary. Careful attention to the adverse consequences associated with these interventions, a limiting factor in many currently available therapies, will be mandatory. Disease modification by biologic agents holds the promise of ushering in an entirely new, more selective approach to therapy. A number of these biologic agents are currently at the threshold of clinical evaluation. In all likelihood, the scientific knowledge of pathogenic mechanisms operative in the rheumatic diseases gained through the use of these agents will be of equal importance to the therapeutic benefits.     

Statins and lower mortality in rheumatic diseases: An effect of immortal time bias?

ObjectiveRandomized controlled trials of the effectiveness of statins on rheumatic disease outcomes have shown limited or no benefit. On the other hand, observational studies have reported remarkable effectiveness of statins at reducing mortality in patients with rheumatic diseases. We evaluated these observational studies for the presence of immortal time bias, which tends to exaggerate the effectiveness of drugs by creating a survival advantage for exposed patients.MethodsWe searched PubMed for observational studies investigating the impact of statins in patients with common rheumatic diseases, including rheumatoid arthritis, osteoarthritis, lupus, ankylosing spondylitis, gout and systemic autoimmune diseases. Studies were included if estimates for all-cause mortality among statin users compared to non-users were reported. We evaluated each study for the presence of immortal time bias and estimated the impact of the bias on the published results.ResultsWe found eight observational studies investigating the impact of statins on mortality among patients with rheumatic diseases. Four studies were affected by the classical variant of immortal time bias, while the others introduced immortal time into the comparator via random-calendar date assignment. The studies with the classical form of immortal time bias, which tends to exaggerate drug effectiveness, reported protective effects of statins on mortality ranging from 13% to 57% reductions. In contrast, immortal time bias through random-calendar date assignment, which tends to play down the effectiveness by introducing immortal time in the comparator, reported 16% to 37% reductions in mortality.ConclusionBias in observational studies may explain the discrepancy in findings with randomized controlled trials on the effectiveness of statins in patients with rheumatic diseases. Future observational studies will need to rely on incident and prevalent new-user designs that emulate randomized trials and avoid immortal time bias.     

A systematic review of randomized controlled trials of acupuncture for neck pain.

OBJECTIVE: To establish whether there is evidence for or against the efficacy of acupuncture in the treatment of neck pain. METHODS: A systematic literature review was undertaken of studies that compared needle or laser acupuncture with a control procedure for the treatment of neck pain. Two reviewers independently extracted data concerning study methods, quality and outcome. RESULTS: Overall, the outcomes of 14 randomized controlled trials were equally balanced between positive and negative. Acupuncture was superior to waiting-list in one study, and either equal or superior to physiotherapy in three studies. Needle acupuncture was not superior to indistinguishable sham control in four out of five studies. Of the eight high-quality trials, five were negative. CONCLUSIONS: In conclusion, the hypothesis that acupuncture is efficacious in the treatment of neck pain is not based on the available evidence from sound clinical trials. Further studies are justified.     

Effectiveness of transcutaneous electrical nerve stimulation for treatment of hyperalgesia and pain

Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacologic treatment for pain relief. TENS has been used to treat a variety of painful conditions. This review updates the basic and clinical science regarding the use of TENS that has been published in the past 3 years (ie, 2005–2008). Basic science studies using animal models of inflammation show changes in the peripheral nervous system, as well as in the spinal cord and descending inhibitory pathways, in response to TENS. Translational studies show mechanisms to prevent analgesic tolerance to repeated application of TENS. This review also highlights data from recent randomized, placebo-controlled trials and current systematic reviews. Clinical trials suggest that adequate dosing, particularly intensity, is critical to obtaining pain relief with TENS. Thus, evidence continues to emerge from both basic science and clinical trials supporting the use of TENS for the treatment of a variety of painful conditions while identifying strategies to increase TENS effectiveness.