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Final evidence for the overall benefits of exercise therapy in the treatment/rehabilitation of specific chronic disease comes from randomized controlled trials (RCTs). This paper summarizes current evidence that is based on a systematic review including data from at least three RCTs with contrast for exercise only. The quality of specific RCTs as well as the quality of systematic reviews varies, the newest ones usually being of higher quality than the older ones. The most consistent finding of the studies is that aerobic capacity and muscular strength of patients can be improved without causing detrimental effects on disease progression. Severe complications during these carefully tailored programs were rare. The treatment periods and follow-up times of the majority of the RCTs are of a too short duration to document group differences in disease progression. However, exercise reduces disease-related symptoms in many diseases, such as osteoarthritis, asthma and chronic obstructive pulmonary disorder. Also, RCTs studying patients with coronary heart disease as well as patients with heart failure show that all-cause mortality is lower in exercisers than in controls.
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PMID:Evidence for exercise therapy in the treatment of chronic disease based on at least three randomized controlled trials--summary of published systematic reviews. 1664 91

The two cyclooxygenase isoforms (COX-1 and COX-2--coxibs) have overlapping functions and both are involved in the regulation of homeostatic and inflammatory processes in the various tissues. Treatment with highly selective COX-2 inhibitors is associated with significantly fewer serious adverse gastrointestinal events than is treatment with the dual inhibitors--the non-selective NSAIDs. Of the two coxibs, rofecoxib was shown to be much more selective than celecoxib and with less interaction with other drugs. Various clinical studies have demonstrated that the coxibs are equivalent, in anti-inflammatory, analgesic and antipyretic efficacy to comparator non-selective NSAIDs in osteoarthritis, rheumatoid arthritis, post surgery pain and dysmenorrhea. Perioperative use of coxibs reduces pain, opioid consumption and the risk of bleeding caused by the non-selective NSAIDs. The coxibs show similar tolerability for renal, liver and cardiothrombotic events as compared to the non-selective NSAIDs. Coxibs are contraindicated in pregnancy, in nursing mothers and pediatric patients and should be used with caution in patients with asthma. The impact of the coxibs on the cardiovascular system is controversial. However, coxibs should be used in caution and at the lowest recommended dose in patients with hypertension, ischemic heart disease and heart failure. These drugs do not interfere with the aspirin anti-platelet aggregation activity. Emerging evidence suggest that the coxibs may also find potential use as supportive therapy in various malignant tumors and intestinal polyps where COX-2 is overly expressed.
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PMID:[Is there a future for COX-2 inhibitors?]. 1560 72

Owing to the selective inhibition of PGI2 synthesis, treatment with COX-2 inhibitors constitutes a potential risk for the increased occurrence of thrombotic cardiovascular incidents and of the first-time occurrence or a deterioration in pre-existing heart failure. Elderly patients, particularly those with a history of ischemic heart disease, hypertension or heart failure, are at risk. One key indication for selective COX-2 inhibitors is the chronic treatment of patients suffering from rheumatoid arthritis or osteoarthritis. However, these patients have an excess cardiovascular mortality, which relates particularly to cardiovascular incidents or heart failure. The use of nonselective antiphlogistic drugs and COX-2 inhibitors is associated with a higher potential risk in these patient groups. In essence, more than 80 million patients worldwide were treated with rofecoxib up to its voluntary withdrawal. The high number of patients who are still being treated with COX-2 inhibitors or for whom the use of COX-2 inhibitors is planned justifies the use of a biochemical marker which, as a screening instrument, is initially designed to recognize the patients who are "ill" despite the lack of symptoms. In asymptomatic patients with NT-proBNP levels below the cut-off, high-risk patients require further work-up. Recognition of these risk factors is easily accomplished considering the case history and the results of an established cardiovascular risk score (e.g. PROCAM score). These risk patients should then also be referred for intensive diagnostic work-up. On the other hand, symptomatic patients or those with high NT-proBNP levels should primarily be referred for more extensive cardiovascular diagnosis before a decision is taken concerning the use of COX-2 inhibitors. As an integral part of this extensive work-up the determination of NT-proBNP can help to improve the accuracy of diagnosis and prognostic assessment. With the exception of patients showing symptoms of an unstable coronary heart disease, imminent cerebral ischemia, uncontrolled arterial hypertension or decompensated heart failure, the use of a COX-2 inhibitor is possible provided special caution is exercised. Termination of treatment is advisable if there is a clinical deterioration of specific symptoms or signs in those patients (product information). Follow-up with NT-proBNP (monitoring) can be helpful in detecting imminent cardiac decompensation at an earlier stage in order to take suitable countermeasures.
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PMID:Rationale for testing the cardiovascular risk for patients with COX-2 inhibitors on the basis of biomarker NT-proBNP. 1571 8

Chronic pain in the elderly is frequently a result of arthritic disorders, particularly osteoarthritis. The cyclo-oxygenase (COX)-2 inhibitors are as effective as standard NSAIDs for the relief of pain and for improving function in elderly patients with osteoarthritis and rheumatoid arthritis. COX-2 inhibitors increase the risk of serious gastroduodenal adverse reactions but there is evidence that they carry a lower risk for these adverse effects than standard NSAIDs, except when there is concurrent aspirin use. Since gastroduodenal disorders are the most frequently reported serious adverse effects of NSAIDs and these disorders occur more frequently in the elderly, COX-2 inhibitors offer an alternative to standard NSAIDs in this age group. However, they are not appropriate for many patients with cardiovascular and renal disease. The adverse reaction profile of the COX-2 inhibitors has confirmed the role of the COX-2 enzyme in renal function, salt and water homeostasis and the vascular endothelium. Thus, like standard NSAIDs, COX-2 inhibitors can cause renal failure, hypertension and exacerbation of cardiac failure. Of note is that these disorders are dose related. Thus, there are good reasons to avoid high doses of COX-2 inhibitors in the elderly. Clinical trials indicate that daily doses of rofecoxib 12.5 mg, celecoxib 100-200 mg, valdecoxib 10mg and etoricoxib 60 mg are the minimum effective doses of these agents. Data from the New Zealand Intensive Medicines Monitoring Programme indicate that celecoxib 200 mg/day and rofecoxib 25 mg/day are/were the most commonly prescribed doses and that 6% of patients had taken rofecoxib 50 mg/day for longer than recommended. Recent research indicates that COX-2 inhibitors have a thrombotic potential, especially in high doses and when use is prolonged, and this further limits the extent to which they can be used in the elderly. Important interactions with COX-2 inhibitors in the elderly include those with warfarin, which can result in loss of control of anticoagulation, and those with ACE inhibitors, angiotensin II type 1 receptor antagonists and diuretics, which can result in loss of control of blood pressure and cardiac failure and, in hypovolaemic conditions, renal failure. The clinical significance of an interaction between celecoxib and aspirin to reduce the antiplatelet effect of the latter drug is unknown. Preliminary information from spontaneous reporting systems indicates that there may be differences in the risk of cardiac failure and hypertension between standard NSAIDs and COX-2 inhibitors and between rofecoxib and celecoxib. More formal studies using equivalent doses are needed to test this observation. Use of COX-2 inhibitors may be considered in the elderly to reduce the risk of gastroduodenal complications associated with standard NSAIDs but only when consideration has first been given to use of less toxic medicines as alternatives or supplements, the appropriate dose of the COX-2 inhibitor or standard NSAID, the presence and possible impact of co-morbidities, and the implications of taking COX-2 inhibitors with any concomitant medications. Equally important is regular monitoring of the patient taking a COX-2 inhibitor for efficacy and adverse effects, and ensuring that the patient has a continuing need to keep taking the drug. Close attention also needs to be paid to intercurrent illnesses and new prescriptions that may reduce the safety of the COX-2 inhibitor. A standard NSAID plus a proton pump inhibitor may be equally effective as a COX-2 inhibitor in reducing the risk of gastroduodenal toxicity and if used the same prescribing advice applies. Current knowledge concerning the thrombotic potential of COX-2 inhibitors suggests that this combination, if tolerated, may be preferable to a COX-2 inhibitor, particularly where prolonged use is required. This knowledge also indicates that for patients with or at high risk of ischaemic heart disease or stroke, COX-2 inhibitors are contraindicated.
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PMID:Cyclo-oxygenase-2 inhibitors: when should they be used in the elderly? 1581 52

Depression is an important but inadequately diagnosed mood disorder in elderly. Depressed elderly patients often have chronic concomitant diseases. This paper intended to determine the prevalence of depression and its relation with concomitant disorders and social status among the patients admitted to our geriatric unit. Seven hundred and eighty-nine females and 466 males admitted to our unit were examined for the presence of depression by using the geriatric depression scale (GDS) test. The presence of concomitant diseases was assessed. Depression was diagnosed in 273 patients (21.8%), 193 (70.7%) females and 80 (29.3%) males. Depressed patients suffered from a wide range of other diseases the number and prevalence of which were as follows: Alzheimer's disease (AD) (34; 12.5%), vascular dementia (27; 9.9%), hypertension (HT) (211; 77.3%), diabetes mellitus (DM) (64; 23.4%), osteoporosis (182; 66.7%), atherosclerotic coronary artery disease (CAD) (89; 32.6%), cardiac failure (23; 8.5%), bronchial asthma (8; 2.9%), chronic obstructive pulmonary disease (COPD) (25; 9.2%) and osteoarthritis (133; 48.8%). The correlation between depression and concomitant diseases was statistically significant in hypertensive, demented and osteoporotic patients, as determined in a large elderly population. Previous studies examined the correlation of depression with only one concomitant disease, while we performed the analysis on multiple correlations.
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PMID:Depression and concomitant diseases in a Turkish geriatric outpatient setting. 1581 64

The objective was to improve understanding of adverse events occurring with celecoxib in the treatment of osteoarthritis and rheumatoid arthritis. Data were extracted from company clinical trial reports of randomised trials of celecoxib in osteoarthritis or rheumatoid arthritis lasting 2 weeks or more. Outcomes were discontinuations (all cause, lack of efficacy, adverse event, gastrointestinal adverse event), endoscopically detected ulcers, gastrointestinal or cardio-renal events, and major changes in haematological parameters. The main comparisons were celecoxib (all doses) versus placebo, paracetamol (acetaminophen) 4,000 mg daily, rofecoxib 25 mg daily, or nonsteroidal anti-inflammatory drugs (NSAIDs) (naproxen, diclofenac, ibuprofen, and loxoprofen). For NSAIDs, celecoxib was compared both at all doses and at licensed doses (200 to 400 mg daily). Thirty-one trials included 39,605 randomised patients. Most patients had osteoarthritis and were women of average age 60 years or above. Most trials lasted 12 weeks or more. Doses of celecoxib were 50 to 800 mg/day. Compared with placebo, celecoxib had fewer discontinuations for any cause or for lack of efficacy, fewer serious adverse events, and less nausea. It had more patients with dyspepsia, diarrhoea, oedema, more adverse events that were gastrointestinal or treatment related, and more patients experiencing an adverse event. There were no differences for hypertension, gastrointestinal tolerability, or discontinuations for adverse events. Compared with paracetamol, celecoxib had fewer discontinuations for any cause, for lack of efficacy, or diarrhoea, but no other differences. Compared with rofecoxib, celecoxib had fewer patients with abdominal pain and oedema, but no other differences. Compared with NSAIDs, celecoxib had fewer symptomatic ulcers and bleeds, endoscopically detected ulcers, and discontinuations for adverse events or gastrointestinal adverse events. Fewer patients had any, or a gastrointestinal, or a treatment-related adverse event, or vomiting, abdominal pain, dyspepsia, or reduced haemoglobin or haematocrit. Discontinuations for lack of efficacy were higher. No differences were found for all-cause discontinuations, serious adverse events, hypertension, diarrhoea, nausea, oedema, myocardial infarction, cardiac failure, or raised creatinine. Company clinical trial reports present much more information than published papers. Adverse event information is clearly presented in company clinical trial reports, which are an ideal source of information for systematic review and meta-analysis.
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PMID:Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheumatoid arthritis: systematic review and meta-analysis of information from company clinical trial reports. 1589 51

Considerable knowledge has accumulated in recent decades concerning the significance of physical activity in the treatment of a number of diseases, including diseases that do not primarily manifest as disorders of the locomotive apparatus. In this review we present the evidence for prescribing exercise therapy in the treatment of metabolic syndrome-related disorders (insulin resistance, type 2 diabetes, dyslipidemia, hypertension, obesity), heart and pulmonary diseases (chronic obstructive pulmonary disease, coronary heart disease, chronic heart failure, intermittent claudication), muscle, bone and joint diseases (osteoarthritis, rheumatoid arthritis, osteoporosis, fibromyalgia, chronic fatigue syndrome) and cancer, depression, asthma and type 1 diabetes. For each disease, we review the effect of exercise therapy on disease pathogenesis, on symptoms specific to the diagnosis, on physical fitness or strength and on quality of life. The possible mechanisms of action are briefly examined and the principles for prescribing exercise therapy are discussed, focusing on the type and amount of exercise and possible contraindications.
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PMID:Evidence for prescribing exercise as therapy in chronic disease. 1664 91

Alkaptonuria (endogenous ochronosis) is a rare metabolic disorder caused by a deficiency of homogentisic acid oxidase, an enzyme responsible for the metabolic degradation of tyrosine. Patients with alkaptonuria commonly present with joint pain owing to degenerative arthritis. Other affected patients may present with pigmentation of the ear cartilage and sclera. This article reports a case of aortic stenosis associated with ochronosis in a 48-year-old man who presented with severe cardiac failure. He had no previous diagnosis of alkaptonuria, which was confirmed by mass spectrometry analysis of urine. The pathogenesis of cardiovascular ochronosis is unclear, but is probably related to the extensive extracellular deposits of ochronotic pigment in the cardiac tissue.
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PMID:Aortic stenosis in cardiovascular ochronosis. 1721 54

(1) Paracetamol is the first-choice analgesic for joint pain. Nonsteroidal antiinflammatory drugs (NSAIDs), especially ibuprofen, are second-line options. Cox-2 inhibitors are no more effective than traditional NSAIDs and have no tangible advantages in terms of gastrointestinal tolerability. In contrast, they expose patients to an increased risk of cardiovascular adverse effects. (2) Etoricoxib is marketed in some European countries to relieve symptoms of osteoarthritis, rheumatoid arthritis, and gout attacks. (3) Many clinical trials have tested etoricoxib in these indications, as well as in ankylosing spondylitis, low back pain, and various types of acute pain. Etoricoxib was no more effective than other NSAIDs such as ibuprofen, naproxen or diclofenac in these situations. (4) Comparative trials showed a higher overall mortality rate with etoricoxib than with naproxen. A combined analysis of long-term comparative trials including 5441 patients, mainly versus naproxen, showed that etoricoxib does not reduce the risk of perforation, ulcer or severe gastrointestinal haemorrhage. Similarly, it does not reduce the risk of mild gastrointestinal events in at-risk patients: those with a history of gastrointestinal disorders, aspirin use, etc. (5) Three trials including a total of 34 701 patients (MEDAL programme) compared cardiovascular thrombotic events associated with etoricoxib and diclofenac. Overall, the cardiovascular risks appear to be similar but the thrombotic risk may be slightly higher with diclofenac than with other conventional NSAIDs. (6) Etoricoxib provoked arterial hypertension, oedema and heart failure during clinical trials. Serious skin reactions were reported both during clinical trials and after marketing, but their precise incidence is not known. Etoricoxib is partly metabolised by the cytochrome P450 isoenzyme CYP 3A4 and increases the bioavailability of ethinylestradiol. (7) When a NSAID is considered, drugs with which we have the most experience should be chosen, such as ibuprofen, and used at the lowest acceptable dose regimen (daily dose and length of treatment). Etoricoxib should be avoided.
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PMID:Etoricoxib: new drug. Avoid using cox-2 inhibitors for pain. 1808 59

Over the past 20 years obesity has become a worldwide concern of frightening proportion. The World Health Organization estimates that there are over 400 million obese and over 1.6 billion overweight adults, a figure which is projected to almost double by 2015. This is not a disease restricted to adults - at least 20 million children under the age of 5 years were overweight in 2005 (WHO 2006). Overweight and obesity lead to serious health consequences including coronary artery disease, stroke, type-2 diabetes, heart failure, dyslipidemia, hypertension, reproductive and gastrointestinal cancers, gallstones, fatty liver disease, osteoarthritis and sleep apnea (Padwal et al 2003). Modest weight loss in the obese of between 5% and 10% of bodyweight is associated with improvements in cardiovascular risk profiles and reduced incidence of type 2 diabetes (Goldstein 1992; Avenell et al 2004; Padwal and Majumdar 2007). Orlistat, a gastric and pancreatic lipase inhibitor that reduces dietary fat absorption by approximately 30%, has been approved for use for around ten years (Zhi et al 1994; Hauptman 2000). There is now a growing body of evidence to suggest that Orlistat assists weight loss and that it may also have additional benefits. The aim of this review is to provide a brief update on the current literature studying the efficacy, safety and significance of the use of Orlistat in clinical practice.
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PMID:Obesity management: update on orlistat. 1820 Aug 2


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