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PARECOXIB IMPAIRS EARLY TENDON REPAIR BUT IMPROVES LATER REMODELING

Background: Cyclooxygenase inhibitors may inhibit bone repair through their action on the bone morphogenic protein system – their effect on tendon repair is not known.

Research question/s: Do cyclooxygenase inhibitors negatively affect early tendon repair?

Methodology::Subjects: Eighty rats that underwent an Achilles tendon transection.

Experimental procedure: Rats were randomly allocated to the following study groups according to drug administration 6.4 mg/kg body weight parecoxib (PC) daily or placebo (PL) – saline), timing of administration, and timing of sacrifice (8–14 days post injury): (1) PL0-5 D8 (PL days 0–5 sacrifice day 8 = 9); (2) PA0-5 D8 (PC days 0–5 sacrifice day 8 = 10); (3) PL0-5 D8 (PL days 0–5 sacrifice day 14 = 10); (4) PA0-5 D8 (PC days 0–5 sacrifice day 14 = 10); (5) PL6-14 D14 (PL days 6–14 sacrifice day 14 = 10); (6) PA6-14 D14 (PC days 6-14 sacrifice day 14 = 10). Tissue was subjected to biomechanical testing and histological analysis on day of sacrifice.

Measures of outcome: Biomechanical data at failure: (force (N), stiffness (N/mm), energy (N.mm), area (mm2), stress (MPa)), histological callus tissue maturity.

Main finding/s:


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  • Day 8: early PC treatment caused a 27% decrease in force at failure (p  =  0.007), a 25% decrease in maximum stress (p  =  0.01), and a 31% decrease in energy uptake (p  =  0.05)

  • Day 14: early PC treatment caused a decrease in stiffness (p  =  0.004), while late PC treatment caused a 16% decrease in cross-sectional area (p  =  0.03) and a 29% increase in maximum stress (p  =  0.04)

Conclusion/s:

  • During early (day 0–5) tendon repair following an acute tendon transection in an animal model, the administration of a cyclooxygenase-2 inhibitor has a detrimental effect on healing, but later administration (after 5 days) resulted in improved healing of tendon tissue

  • Cyclooxygenase-2 inhibitors should be used with care in the early period after tendon injury

Evidence based rating : 8/10

Clinical interest rating : 8/10

Type of study : Randomised controlled laboratory animal study

Methodological considerations : Well conducted study, application to human tissue needs to be verified

Keywords : non-steroidal anti-inflammatory drug (NSAID), tendon repair, ligament, rat, remodelling

COMMUNITY PULMONARY REHABILITATION AFTER HOSPITALISATION FOR ACUTE EXACERBATIONS OF COPD: RANDOMISED CONTROLLED STUDY

Background: The effects of early pulmonary rehabilitation in the recovery phase following and acute exacerbation has not been studied.

Research question/s: Does an early pulmonary rehabilitation programme after hospitalisation for acute exacerbations of chronic obstructive pulmonary disease (COPD) improve exercise capacity, respiratory health, and general health parameters?

Methodology::Subjects: Forty-two COPD patients admitted with an acute exacerbation.

Experimental procedure: Subjects were randomised into two groups: (1) usual care control group (CON  =  16), and (2) 8 week, pulmonary rehabilitation programme ((60 min exercise, 60 min education) 2/week) (REH  =  18) starting within 10 days of hospital discharge. Assessments at hospital discharge and 3 months post discharge.

Measures of outcome: Exercise capacity (shuttle walk distance), respiratory health status (St George’s respiratory questionnaire (SGRQ)); chronic respiratory questionnaire (CRQ), general health status (medical outcomes short form 36 questionnaire (SF-36)).

Main finding/s:


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Respiratory health and general status: the REH group had significantly greater improvements in the mean SGRQ total score (p  =  0.002), in all four domains (dyspnea, fatigue, emotion, mastery) (p < 0.05) of the CRQ score, and the mental component score of the SF-36 (p  =  0.02) but not the physical component (p  =  0.057).

Conclusion/s: A pulmonary rehabilitation programme consisting of regular exercise training and education, started within 10 days after admission to hospital for acute exacerbations of COPD, is safe and significantly improves exercise capacity and health status measured after 3 months.

Evidence based rating: 7/10

Clinical interest rating: 8/10

Type of study: Randomised controlled clinical trial

Methodological considerations: No mechanisms studied, not a double-blind design, small sample size, short-term follow-up

Keywords: COPD, rehabilitation, lung disease, exercise

SUDDEN DEATH IN YOUNG ADULTS: A 25 YEAR REVIEW OF AUTOPSIES IN MILITARY RECRUITS

Background: Sudden death during exercise among military recruits is rare but can provide information that can be very helpful to promote health care policy to reduce the incidence of sudden death in the general population.

Research question/s: What are the causes of non-traumatic sudden death among military recruits undergoing basic training?

Methodology::Subjects: 6.3 million recruits undergoing basic military training (male and female, 18–35 years).

Experimental procedure: All non-traumatic sudden deaths that occurred in recruits undergoing basic military training between 1977 and 2001 in the USA military were monitored. Autopsy reports were available for most (97%) of the 126 deaths that were recorded.

Measures of outcome: Crude mortality rates (deaths/100 000 recruit years), causes of sudden death, and frequency of events as a function of cause of death.

Main finding/s:


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  • Crude mortality rate: 13.0/100 000 recruit-years) with 108 (86%) that were related to exercise

  • Cause of death: cardiac abnormality (64/126 recruits – 51%), unexplained deaths (44/126 recruits – 36%)

  • Frequency of prodromal symptoms (%): coronary artery pathology (31% – syncope, chest pain, dyspnea mostly), myocardial abnormalities (22% – infection related, syncope), idiopathic cause of death (4%)

Conclusion/s: A cardiac abnormality (mostly anomalous coronary arteries, myocarditis, and coronary artery disease) is the most common cause of sudden death among military recruits – importantly about one third of sudden deaths have no identifiable cause.

Evidence based rating: 7.5/10

Clinical interest rating: 9/10

Type of study: Retrospective cohort study

Methodological considerations: Retrospective data, pre-enlistment screening may have altered outcomes

Keywords: sudden death, exercise, non-traumatic, military recruits

CHONDROPROTECTIVE ACTIVITY OF N-ACETYLGLUCOSAMINE IN RABBITS WITH EXPERIMENTAL OSTEOARTHRITIS

Background: Glucosamine, a nutritional supplement, is used in patients with osteoarthritis (OA) as it may modify disease activity (delaying progressive joint space narrowing, improving biomechanics of OA knee joints).

Research question/s: What is the therapeutic efficacy of N-acetylglucosamine (GlcNAc) in rabbits with experimentally induced cartilage degeneration?

Methodology::Subjects: Fifty-seven rabbits that underwent anterior cruciate ligament transection (ACLT) followed by 8 weeks free activity to induce articular cartilage degeneration.

Experimental procedure: Rabbits were randomly allocated to the following groups: (1) receiving intramuscular injections of N-acetylglucosamine (GlcNAc) 3/week (GLCimi group  =  6); (2) normal saline 3/week three times a week (SALimi  =  6); (3) intra-articular injection with GlcNAc (1-2/week) (GLCiai1  =  8); (4) intra-articular saline (SALiai  =  8); (5) intra-articular GlcNAc 2/week (GLCiai2  =  7); (6) intra-articular hyaluronan 2/week (HYLiai  =  7); and (7) intra-articular normal saline 2/week (SALiai2  =  7). Animals were killed at 8 weeks and tissue was analysed.

Measures of outcome: Macroscopic and histological assessment of the knee joint.

Main finding/s:


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  • Intramuscular administration: there was no significant chondroprotective effects in the GLCimi group but there was mild anti-inflammatory activity in the GLCimi group

  • Intra-articular administration: there was reduced cartilage degradation and suppressed synovitis in the GLCimi2 (injected 2/week) group but not in the GLCiai group (injected 1/week). The chondroprotective efficacy of GLCimi2 was greater than the HYLiai group

Conclusion/s: Intra-articular, but not intra-muscular injection of GlcNAc (2/week) has chondroprotective and anti-inflammatory activity in experimentally induced cartilage degeneration in animals.

Evidence based rating: 7.5/10

Clinical interest rating: 7/10

Type of study: Randomised controlled clinical trial (experimental animal study)

Methodological considerations: Well conducted study, animal model outcomes

Keywords: knee, osteoarthritis, glucosamine, hyaluronic acid

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