Lawrence E. Hart

Is regular exercise a friend or foe of the aging immune system? A systematic review

Objective:The purpose of the current review is to synthesize the available evidence from prospective clinical trials that are relevant to the clinical question: “What, if any, are the effects of regular aerobic and/or resistance exercise on the immune system in healthy older adults?” Data Sources:Electronic databases were searched, using terms pertaining to immunology, exercise, and aging. Using the Ovid interface, the following databases were explored: Allied and Complimentary Medicine (AMED) (1985 to 2008), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 2008), all EBM Reviews (Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED), EMBASE (1980 to 2008), and MEDLINE (1950 to 2008). The MEDLINE database was searched a second time through the PubMed interface. Study Selection:Prospective controlled clinical trials were selected for review if they investigated the effects of an exercise intervention (minimum 4 weeks in duration) on an immune outcome measure in an older but otherwise healthy population. A total of 19 articles representing 17 trials were identified. Data Extraction:Quality assessment of the relevant articles was performed using the Jadad et al1 criteria. Data extraction was performed using a standardized instrument. Data regarding the participants, interventions, and laboratory and clinical immunologic outcomes were synthesized. Data Synthesis:Available data provide no clear evidence of acute or chronic effects of exercise on lymphocyte or natural killer (NK) cell numbers or phenotype (ie, surface markers)/activity, with 2 exceptions: (1) strength or endurance exercise may cause an acute transient elevation in circulating CD8+ T cells, and (2) regular aerobic exercise appears to enhance immunologic memory in the context of vaccination. The effects of strength training on NK cell activity are unclear. Furthermore, regular aerobic exercise appears to be associated with a reduction in chronic inflammation. Finally, no prospective controlled trials have clearly documented clinical immunologic benefits of regular exercise, which may well relate to underpowering of these studies. Conclusions:Overall, in healthy older adults, regular, particularly aerobic, exercise appears to be a friend of the immune system, helping to offset diminished adaptive responses and chronic inflammation. The possibility exists that particularly strenuous exercise may cause acute immunologic changes, such as diminished NK cell activity, which could predispose to infection in certain individuals. However, given the possible benefits of regular exercise on the immune system and the many definite benefits on other systems, the evidence presented here should not dissuade practitioners from suggesting regular exercise to otherwise healthy older adults.

Corticosteroid and other injections in the management of tendinopathies: a review.

OBJECTIVE To determine the efficacy and risk of adverse effects of peritendinous corticosteroid and other injections in the management of tendinopathy. DATA SOURCES In March 2010, using terms describing common tendinopathies and injections, including steroids, local anesthetics, sclerosing solutions, aprotinin, platelet-rich plasma, botulinum toxins, and glycosaminoglycans, 8 databases were searched without language, publication, or date restrictions. Reference lists were scanned for additional articles. STUDY SELECTION Criteria for inclusion were randomized controlled trials that compared ≥1 peritendinous injection with placebo or other nonsurgical intervention. Study methods were independently assessed by 2 reviewers (reliability, κ = 0.85) on a modified PEDro scale, and scores were required to be ≥50% for inclusion. Studies with a high proportion of patients with adhesive capsulitis, full-thickness rotator cuff tears, or rheumatologic disease were excluded. Of 2954 studies screened, 174 full-text articles were evaluated for inclusion by 1 investigator and confirmed by a second. Of 64 studies that were initially included, the 41 that scored >50% on the PEDro scale were retained. DATA EXTRACTION Information about injection type and comparison treatments, site of the tendinopathy, duration of follow-up (short term, <12 weeks; long term, ≥52 weeks), outcomes (pain, function, and patient-rated overall improvement), and frequency of adverse events was extracted. Study results were pooled when the data were sufficiently homogeneous. MAIN RESULTS Clinically diagnosed lateral epicondylalgia: In 3 trials that compared corticosteroid injections with no intervention, corticosteroid injections were effective in the short term in pain reduction [standard mean difference (SMD), 1.44; 95% confidence interval (CI), 1.17-1.71], in improving function (SMD, 1.50; 95% CI, 1.22-1.77), and in overall improvement [relative risk (RR), 3.47; 95% CI, 2.11-5.69]. In the intermediate and long term, corticosteroid injections were less effective than no intervention. In comparison with placebo injection (4 studies), there was limited evidence for the effectiveness of corticosteroid injection in relieving pain. In comparison with physiotherapy (4 studies), corticosteroid injection was more effective in the short term for improving function (SMD, 1.29; 95% CI, 1.03-1.55) and in overall improvement (RR, 2.37; 95% CI, 1.75-3.21), and there was strong evidence among heterogeneous studies for reducing pain. Intermediate and long-term results were worse in pain and function for the corticosteroid injection intervention. Corticosteroid injections were more effective than orthotic devices for the wrist or elbow for overall improvement in the short term but not in the long term (2 studies). Effectiveness did not differ in comparisons of high- versus low-corticosteroid dosage, and between triamcinolone and hydrocortisone. Pain and function improved more with corticosteroid than with platelet-rich plasma injection in the short term but were worse in the long term. Rotator cuff tendinopathy: In the short term, corticosteroid injection improved pain (SMD, 0.68; 95% CI, 0.35-1.01) and function (SMD, 0.62; 95% CI, 0.29-0.95) more than placebo (3 studies). In comparisons with nonsteroidal anti-inflammatory drugs (NSAIDs) and with NSAIDs plus placebo injection, no differences in pain or function were found (3 studies) or when NSAIDs were administered in addition to corticosteroid and placebo injections (4 studies). Corticosteroid injection and physiotherapy did not differ in effectiveness (2 studies), although 1 study found short-term greater overall improvement and function after corticosteroid injection. Adverse effects were reported in 82% of corticosteroid injection trials. In comparison with placebo injections, corticosteroid injections were associated with an increased risk of atrophy for Achilles and patellar tendons but not elbow tendons. In trials of injections of sclerosant, platelet-rich plasma, proteinase, glycosaminoglycan polysulfate, sodium hyaluronate, prolotherapy, and botulinum toxin compared with placebo injection or other therapies, only sodium hyaluronate compared with placebo showed consistently better results in the short and long term in overall improvement and pain reduction of lateral epicondylalgia (1 study). Adverse effects were reported for all these injections except sclerosant and platelet-rich plasma. CONCLUSIONS Corticosteroid injection is beneficial in the short term for the treatment of tendinopathies but may be worse than other treatments in the intermediate and long terms. No clear evidence of benefit of other injections was shown, except for sodium hyaluronate in the short and long term.

Effect of stretching on sport injury risk: a review.

Objective:Effect of Stretching on Sport Injury Risk: a Review To assess the evidence for the effectiveness of stretching for the prevention of injuries in sports. Data sources:MEDLINE (1966 to September, 2002), Current Contents, Biomedical Collection, Dissertation Abstracts, the Cochrane Library, and SPORTDiscus were searched for articles in all languages using terms including stretching, flexibility, injury, epidemiology, and injury prevention. Reference lists were searched and experts contacted for further relevant studies. Study selection:Criteria for inclusion were randomized trials or cohort studies of interventions that included stretching compared with other interventions, with participants who were engaged in sporting or fitness activities. One author identified 361 articles reporting on flexibility, methods and effects of stretching, risk factors for injury, and injury prevention, of which 6 articles fulfilled the inclusion criteria for meta-analysis. Data extraction:Three independent reviewers blinded to the authors and institutions of the investigations assessed the methodologic quality of the studies (100-point scale) and reached consensus on disagreements. Details of study participants, interventions, and outcomes were extracted. Weighted pooled odds ratios were calculated for effects of interventions on an intention-to-treat basis. Main results:Reduction in total injuries (shin splints, tibial stress reaction, sprains/strains, and lower-extremity and -limb injuries) with either stretching of specific leg-muscle groups or multiple muscle groups was not found in 5 controlled studies (odds ratio [OR] 0.93; 95% CI, 0.78 to 1.11). Reduction in injuries was not significantly greater for stretching of specific muscles (OR, 0.80; CI, 0.54-1.14) or multiple muscle groups (OR, 0.96; CI, 0.71-1.28). Combining the 3 ratings of methodologic quality, median scores were 29 to 60/100. After adjustment for confounders, low quality studies did not show a greater reduction in injuries with stretching (OR, 0.88; CI, 0.67-1.15) compared with high quality studies (OR, 0.97; CI, 0.77-1.22). Stretching to improve flexibility, adverse effects of stretching, and effects of warm up were not assessed by appropriate intervention studies. Conclusion:Limited evidence showed stretching had no effect in reducing injuries.

Exercise and soft tissue injury.

Once the almost exclusive domain of the orthopaedic surgeon, sports injuries are now being seen with increasing frequency by other specialists, including rheumatologists. It is therefore important for rheumatologists to be able to diagnose and manage the various musculoskeletal conditions that are associated with physical activity. Soft tissue injuries are a very common cause of morbidity in both competitive and recreational athletes. Most of these conditions are provoked by muscle-tendon overload (or overuse) that is usually the result of excessive training or improper training techniques. However, despite an emerging literature on the natural history of soft tissue overuse syndromes, relatively little is known about the causes, incidence and outcome of many of these injuries. Of the methodologically robust epidemiological studies that have been done, most have focused on habitual distance runners. In this population, it has been reported that the incidence of injury can be as high as 50% or more, and that overtraining and the presence of previous injury are the most significant predictors of future injury. In other popular forms of exercise, such as walking, swimming, cycling, aerobics and racquet sports, injuries are also reported with high frequency but, to date, no prospective studies have examined actual incidences in these populations, and risk factors for injury in these activities remain speculative. Several of the more commonly occurring soft tissue injuries (such as rotator cuff tendinitis, lateral and medial epicondylitis, patellar tendinitis, the iliotibial band friction syndrome, Achilles tendinitis and plantar fasciitis) exemplify the overuse concept and are therefore highlighted in this review. The management of these, and most other, exercise-related soft tissue injuries is directed towards promptly restoring normal function and preventing re-injury.

The relationship between exercise and osteoarthritis in the elderly.

Objectives:To review within a prescribed evidence-based framework (1) the relationship between intermittent or lifelong physical activity and the subsequent onset or progression of osteoarthritis (OA) in later life and (2) the effect of structured exercise routines on the management of OA in the elderly. Data Sources:A systematic literature search of MEDLINE (1950 to April Week 2, 2008) and EMBASE (1980 to 2008 Week 16) was carried out using the Ovid interface. Relevant mapped terms addressing the identified objectives were combined and exploded according to a defined protocol. Study Selection:Studies that met relevancy criteria and were of high methodologic quality (prospective cohort studies for the risk factor component and systematic reviews and randomized controlled trials for the therapy component) were extracted and then hand searched for any additional studies. Final inclusion was based on agreement between two independent assessors, according to prescribed criteria. Any studies that were not in the English language, did not address the questions of interest in humans, or did not include a population that had at least a mean age of 55 years at the time of study termination, were excluded. Only land-based regimens were included in the therapy component of the review. Data Extraction:Pertinent information on subjects, risks, and outcomes (when assessing physical activity as a risk factor for OA in the elderly) and subjects, interventions, and outcomes (when evaluating the application of exercise in the management of OA in older persons) was extracted from the selected studies. Data Synthesis:Ten studies met entry criteria for examining the relationship between physical activity and the development or progression of OA. Likely because of study variations and differences in the nature, duration and intensities of exercise regimens, no clearcut consensus was apparent on whether or not physical activity was a risk factor for OA. Six scientific reviews and ten single blinded randomized controlled trials were included when evaluating the effect of exercise on OA management. Regardless of wide variability in the included studies, a majority demonstrated that structured exercise programs were effective in the management of older subjects with OA. Conclusions:Nuances of study design, differences in age and type of target populations, variability in the intensity, duration, and nature of physical activity in the respective studies, and lack of standardization in the way radiographic data are interpreted are among the factors that prevent consensus regarding the effect of physical activity on later development of OA. Similarly, there is considerable heterogeneity in the studies that assessed exercise in the treatment of OA. Nonetheless, there is substantive evidence in support of the benefits of one or another strength training or aerobic exercise regimen in the management of OA in middle-aged and elderly subjects.

Training Habits and Injury Experience in Distance Runners: Age- and Sex-Related Factors.

In brief: An 80-item questionnaire was used to study the variations by age and sex in the training habits and injury experience of 688 adult entrants in a 10-mile road race in southern Ontario. The results showed that runners over the age of 30 years tend to train at a slower pace than younger runners. On the average, men trained over somewhat longer distances and at a faster pace than women of the same age, but women ran more times per week. Older athletes tended toward a higher weekly mileage and entered the longer distance races. While 57% of all respondents reported at least one injury during the 12 months preceding our study, there was no significant variation by age or sex.

Marathon-related cardiac arrest.

OBJECTIVE To investigate the incidence and assess the outcomes of cardiac arrest occurring in the context of participation in marathon or half-marathon races. DESIGN Incidence study. SETTING Data came from long-distance race records in the United States from January 1, 2001, to May 31, 2010. PARTICIPANTS All participants were registered entrants in the long-distance races. Participation statistics (sex, participant identity numbers, and race distance) were publicly accessible from Running USA. ASSESSMENT OF RISK FACTORS Data on possible risk factors for cases were obtained retrospectively through computer searches (age, sex, location of cardiac arrest, publicly released cause of death). Three attempts were made to obtain information from survivors or from the next-of-kin of deceased cases. This information included demographic characteristics, exercise and running history, and personal and family medical history. MAIN OUTCOME MEASURES The main outcome measures were the incidence and characteristics of cases of cardiac arrest that occurred during the race, at the finish-line, or ≤ 1 hour after completion of a marathon or half marathon. Cardiac arrests were defined by a medical professional as an unconscious state and an absence of spontaneous respirations and pulse. Successful resuscitation and discharge from hospital defined a survivor, whereas a nonsurvivor was a person who was not successfully resuscitated in the field or who died before hospital discharge. Cases of cardiac arrest had to be independently identified in 3 separate sources of data or confirmed with official race medical staff. Further information, including details of the cardiac arrest, was obtained from medical records and autopsies and the survivors or next of kin. MAIN RESULTS Among 10.9 million registered race participants there were 40 cardiac arrests in marathons and 19 in half marathons (overall incidence, 0.54 per 100,000; 95% confidence interval [CI], 0.41-0.70). The mean age of runners with cardiac arrest was 42 (SD 13) years and 86% were men. The incidence per 100,000 was higher in marathons (1.01; 95% CI, 0.72-1.38) than in half marathons (0.27; 95% CI, 0.17-0.43; and among men (0.90; 95% CI, 0.67-1.18) than among women (0.16; 95% CI, 0.07-0.31). More runners died than survived the cardiac arrest (42 [71%] vs 17[29%]); the incidence of sudden death was 0.39 per 100,000 participants (95% CI, 0.28-0.52). The mean age of the nonsurvivors was younger than that of the survivors (39 vs 49 years; P = 0.002). Complete clinical information on cause of death was available for 23 runners. The most common confirmed or possible cause of death was hypertrophic cardiomyopathy (15 cases, of whom 9 had an additional clinical factor). Among the 8 survivors with complete information, ischemic heart disease was the cause of cardiac arrest in 5. The survivors were older than nonsurvivors (53 vs 40 years), had completed more long-distance races, and were more likely to have known cardiac risk factors. The strongest predictors of survival were initiation of cardiopulmonary resuscitation by bystanders (P = 0.01) and an underlying diagnosis other than hypertrophic cardiomyopathy (P = 0.01) CONCLUSIONS:: The incidence of cardiac arrest and sudden death per 100,000 runner hours was 0.2 and 0.14. Risk factors for cardiac arrest were full marathon and male sex. Younger age and no previous knowledge of cardiovascular risk were associated with sudden death.

Quadriceps Strength As A Predictor of Knee Osteoarthritis Progression

ObjectiveTo determine whether quadriceps strength is associated with tibiofemoral osteoarthritis progression in persons with knee osteoarthritis. The association was examined particularly in malaligned knees and high-laxity knees. DesignCohort study. SettingAcademic medical center in Chicago, Illinois. ParticipantsParticipants for a natural history study (Mechanical Factors in Arthritis of the Knee) were recruited through periodicals, organizations, and medical center referrals. Inclusion criteria were osteophyte presence in 1 or both knees and difficulty with ≥2 items in the Western Ontario and McMaster University osteoarthritis index physical function scale. Exclusion criteria were corticosteroid injection within 3 months, inflammatory arthritis, comorbidity in the lower limb, and replacement or planned replacement of the arthritic knee(s). Of 237 participants, 230 were followed for 18 months, and 171 (mean age, 64 years; 74% women) who did not have advanced osteoarthritis at baseline (Kellgren and Lawrence grade 4) were included in the analysis (328 knees). Assessment of risk factorsBaseline measurements were obtained for both knees. Isokinetic quadriceps strength (maximal torque during movement) was assessed by means of a computer-driven isokinetic dynamometer. Alignment was measured on a single anterior radiograph of both lower extremities. A knee was considered malaligned if the angle of the intersection of the line between the centers of the femoral head and inter-condylar notch and the line between the centers of the ankle talus and tibial spines was 5° or more. High varus-valgus laxity (the sum of varus and valgus rotation for each knee measured at the foot) was defined as knees in the highest tertile (≥5.75°). Main outcome measuresThe main outcome measure was tibiofemoral osteoarthritis progression (an increase in the grade of joint space narrowing) determined radiographically at baseline and 18 months. Main resultsThe predicted probability of arthritis progression, after adjustment for baseline age, body mass index, disease severity, and physical activity, was slightly greater in knees with greater quadriceps strength (>47.3 ft-lb) compared with lesser quadriceps strength (0.153 vs. 0.098; P = 0.09). In logistic regression, strength was associated with an increase in predicted probability of disease progression in malaligned knees (n = 78; high strength, 0.406. vs. low strength, 0.187; P = 0.03), but not in neutrally aligned knees (n = 250; P > 0.2). High strength in the knees with high laxity (≥5.75°; n = 110) and in knees with the greatest laxity (≥6.75°; n = 70) was associated with a greater probability of arthritis progression (P = 0.05 and P = 0.003, respectively). ConclusionsQuadriceps strength was not found to be beneficial in reducing the progression of tibiofemoral knee osteoarthritis in older adults. Quadriceps strength was predictive of more severe arthritis progression in malaligned knees and in knees with high laxity.

Evidence in context: one person’s poison is another’s acceptable risk

Seeing a patient who might be having an adverse effect of a medication may lead to a clash of perspectives. For example, from the viewpoint of a cardiologist caring for someone with an acute coronary syndrome, it is all too easy to blame the internist or rheumatologist who prescribed a cyclo-oxygenase-2 (COX-2) inhibitor for a patient’s arthritis. This is yet another example of “practice variation,” or slow knowledge translation. However, such a judgement ignores the complexity of the evidence that putatively links COX-2 inhibitors to heart disease. To be sure, there is evidence that COX-2 inhibitors can increase risk of cardiovascular (CV) disease, but what may be overlooked is that the extent of such risk varies substantively among patients, depending on the drug, dose, dosing frequency, duration, and outcome definition. Furthermore, the balance of benefits and risks for patients depends on their unique clinical states and circumstances,1 the success or failure of alternatives, and the patient’s wishes.2 Applying the …

A growing concern: the older athlete.

By the year 2030, in the United States alone, the number of people aged 65 years and older will reach 70 million, with those over 85 constituting the fastest growing segment of all. The promotion of physical activity as a way to treat and prevent disease has therefore become increasingly more important for these older adults. A recurring concept in this thematic issue is that there are very few contraindications to exercise in the elderly. Thus, exercise is medicine and should be enthusiastically—although carefully— prescribed, in one form or another, for almost all of our patients. It is a critical part of the treatment regimen for chronic conditions such as coronary artery disease and osteoarthritis, as well as for common illnesses like depression. Furthermore, the effects of regular physical activity, such as improvements in a person’s functional capacity and quality of life, contribute enormously to a healthier, independent lifestyle. In the current reviews, we have tried to capture the issues most relevant to physicians and other health care providers who deal with older athletes. We hope that increased awareness of their unique needs will promote improved care as well as further research in this special—and growing—population. The primary changes in the cardiovascular system associated with aging are a decrease in elasticity coupled with an increase in stiffness of the arterial system. This alteration in vessel compliance results in increased afterload on the left ventricle, an increase in systolic blood pressure, and left ventricular hypertrophy, as well as other changes in the left ventricular wall that prolong diastolic relaxation. These changes set the stage for isolated systolic hypertension, diastolic dysfunction, atrioventricular conduction defects, and aortic valve calcification—all of which are seen with ever greater frequency in the elderly. Heckman and McKelvie note that many of the age-associated changes in cardiovascular function are not entirely due to aging per se, but rather to a lack of exercise. They go on to provide specific evidence-based strategies that incorporate both aerobic and strength training to optimize cardiovascular function in the healthy elderly. An area of increasing importance in the older athlete is the impact of exercise on cognition and emotional well-being. van Uffelen and colleagues systematically review the evidence that involvement in regular exercise has a number of psychological benefits, including the preservation of cognitive function, the alleviation of depression, and an improvement in aspects of personal control and self-efficacy among subjects both with and without cognitive decline. As pointed out by Faulkner and colleagues, a number of physiologic changes occur in skeletal muscle, starting around age 50 years, that may impact athletic performance. These are not completely age-related, however, and losses are strikingly diminished through strength training. The authors provide specific recommendations to limit age-related sarcopenia and strength losses. The use of such approaches will no doubt present challenges to anyone who is privileged to provide counsel and care to competitive athletes of all ages. In addition, the Faulkner paper seeks to raise our awareness to two genes, IGF-1 and myostatin, as potential targets to increase muscle mass. A question faced everyday by anyone caring for the older athlete is the role of regular exercise in incident and progressive osteoarthritis (OA) Hart and colleagues critically review the EMBASE and MEDLINE databases to shed some light on the fascinating, although controversial, literature on this topic. In the second part of their review they switch constructs—to discuss the application of exercise in the management of older patients with already established OA. The authors end with their suggestions for future studies, including