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Drug Safety Dec 2012The risk of upper gastrointestinal (GI) complications associated with the use of NSAIDs is a serious public health concern. The risk varies between individual NSAIDs;... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The risk of upper gastrointestinal (GI) complications associated with the use of NSAIDs is a serious public health concern. The risk varies between individual NSAIDs; however, there is little information on the risk associated with some NSAIDs and on the impact of risk factors. These data are necessary to evaluate the benefit-risk of individual NSAIDs for clinical and health policy decision making. Within the European Community's Seventh Framework Programme, the Safety Of non-Steroidal anti-inflammatory drugs (NSAIDs) [SOS] project aims to develop decision models for regulatory and clinical use of individual NSAIDs according to their GI and cardiovascular safety.
OBJECTIVE
The aim of this study was to conduct a systematic review and meta-analysis of observational studies to provide summary relative risks (RR) of upper GI complications (UGIC) associated with the use of individual NSAIDs, including selective cyclooxygenase-2 inhibitors.
METHODS
We used the MEDLINE database to identify cohort and case-control studies published between 1 January 1980 and 31 May 2011, providing adjusted effect estimates for UGIC comparing individual NSAIDs with non-use of NSAIDs. We estimated pooled RR and 95% CIs of UGIC for individual NSAIDs overall and by dose using fixed- and random-effects methods. Subgroup analyses were conducted to evaluate methodological and clinical heterogeneity between studies.
RESULTS
A total of 2984 articles were identified and 59 were selected for data abstraction. After review of the abstracted information, 28 studies met the meta-analysis inclusion criteria. Pooled RR ranged from 1.43 (95% CI 0.65, 3.15) for aceclofenac to 18.45 (95% CI 10.99, 30.97) for azapropazone. RR was less than 2 for aceclofenac, celecoxib (RR 1.45; 95% CI 1.17, 1.81) and ibuprofen (RR 1.84; 95% CI 1.54, 2.20); 2 to less than 4 for rofecoxib (RR 2.32; 95% CI 1.89, 2.86), sulindac (RR 2.89; 95% CI 1.90, 4.42), diclofenac (RR 3.34; 95% CI 2.79, 3.99), meloxicam (RR 3.47; 95% CI 2.19, 5.50), nimesulide (RR 3.83; 95% CI 3.20, 4.60) and ketoprofen (RR 3.92; 95% CI 2.70, 5.69); 4-5 for tenoxicam (RR 4.10; 95% CI 2.16, 7.79), naproxen (RR 4.10; 95% CI 3.22, 5.23), indometacin (RR 4.14; 95% CI 2.91, 5.90) and diflunisal (RR 4.37; 95% CI 1.07, 17.81); and greater than 5 for piroxicam (RR 7.43; 95% CI 5.19, 10.63), ketorolac (RR 11.50; 95% CI 5.56, 23.78) and azapropazone. RRs for the use of high daily doses of NSAIDs versus non-use were 2-3 times higher than those associated with low daily doses.
CONCLUSIONS
We confirmed variability in the risk of UGIC among individual NSAIDs as used in clinical practice. Factors influencing findings across studies (e.g. definition and validation of UGIC, exposure assessment, analysis of new vs prevalent users) and the scarce data on the effect of dose and duration of use of NSAIDs and on concurrent use of other medications need to be addressed in future studies, including SOS.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Dose-Response Relationship, Drug; Gastrointestinal Hemorrhage; Humans; Risk Factors
PubMed: 23137151
DOI: 10.2165/11633470-000000000-00000 -
The Cochrane Database of Systematic... Feb 2016Chronic back pain is an important health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic back pain is an important health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people with acute back pain. Short term NSAID use is also recommended for pain relief in people with chronic back pain. Two types of NSAIDs are available and used to treat back pain: non-selective NSAIDs and selective COX-2 NSAIDs. In 2008, a Cochrane review identified a small but significant effect from NSAIDs compared to placebo in people with chronic back pain. This is an update of the Cochrane review published in 2008 and focuses on people with chronic low back pain.
OBJECTIVES
To determine if NSAIDs are more efficacious than various comparison treatments for non-specific chronic low back pain and if so, which type of NSAID is most efficacious.
SEARCH METHODS
We searched CENTRAL, MEDLINE, EMBASE, PubMed and two clinical trials registry databases up to 24 June 2015 for randomized controlled trials (RCTs) published in English, German or Dutch. We also screened references cited in relevant reviews.
SELECTION CRITERIA
We included RCTs (double-blind and single-blind) of NSAIDs used to treat people with chronic low back pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened trials for inclusion in this Cochrane review according to the inclusion criteria. One review author extracted the data, and a second review author checked the data. Two review authors independently evaluated the risk of bias of all included trials. If data were clinically homogeneous, we performed a meta-analysis and assessed the quality of evidence using the GRADE approach.
MAIN RESULTS
We included 13 trials in this Cochrane review. Ten studies were at 'low' risk of bias. Six studies compared NSAIDs with placebo, and included 1354 participants in total. There is low quality evidence that NSAIDs are more effective than placebo, with a mean difference in pain intensity score from baseline of -3.30 (95% CI -5.33 to -1.27) on a 0 to 100 visual analogue scale (VAS) with a median follow-up of 56 days (interquartile range (IQR) 13 to 91 days). Four studies measured disability using the Roland Morris Disability Questionnaire. There is low quality evidence that NSAIDs are more effective than placebo on disability, with a mean difference from baseline of -0.85 (95% CI -1.30 to -0.40) on a scale from 0 to 24 with a median follow-up of 84 days (IQR 42 to 105 days). All six placebo controlled studies also reported adverse events, and suggested that adverse events are not statistically significant more frequent in participants using NSAIDs compared to placebo (RR 1.04, 95% CI 0.92 to 1.17). Due to the relatively small sample size and relatively short follow-up in most included trials, it is likely that the proportion of patients experiencing an adverse event is underestimated.Two studies compared different types of non-selective NSAIDs, namely ibuprofen versus diclofenac and piroxicam versus indomethacin. The trials did not find any differences between these NSAID types, but both trials had small sample sizes. One trial reported no differences in pain intensity between treatment groups that used selective or non-selective NSAIDs. One other trial compared diflunisal with paracetamol and showed no difference in improvement from baseline on pain intensity score. One trial showed a better global improvement in favour of celecoxib versus tramadol.One included trial compared NSAIDs with 'home-based exercise'. Disability improved more in participants who did exercises versus participants receiving NSAIDs, but pain scores were similar.
AUTHORS' CONCLUSIONS
Six of the 13 included RCTs showed that NSAIDs are more effective than placebo regarding pain intensity. NSAIDs are slightly more effective than placebo regarding disability. However, the magnitude of the effects is small, and the level of evidence was low. When we only included RCTs at low risk of bias, differences in effect between NSAIDs and placebo were reduced. We identified no difference in efficacy between different NSAID types, including selective versus non-selective NSAIDs. Due to inclusion of RCTs only, the relatively small sample sizes and relatively short follow-up in most included trials, we cannot make firm statements about the occurrence of adverse events or whether NSAIDs are safe for long-term use.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Diclofenac; Disability Evaluation; Humans; Ibuprofen; Indomethacin; Low Back Pain; Pain Measurement; Piroxicam; Randomized Controlled Trials as Topic
PubMed: 26863524
DOI: 10.1002/14651858.CD012087 -
The Cochrane Database of Systematic... Sep 2015This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events are now dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews and assesses the reliability of available data.
OBJECTIVES
To summarise the efficacy of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery who have been given a single dose of oral analgesic.
METHODS
We identified systematic reviews in the Cochrane Database of Systematic Reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome the number of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews, we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, and the percentage of participants remedicating by six, eight, 12, or 24 hours. Where there was adequate information for pairs of drug and dose (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable.
MAIN RESULTS
The overview included 39 separate Cochrane Reviews with 41 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 50,000 participants in approximately 460 individual studies. The individual reviews included only high-quality trials of standardised design, methods, and efficacy outcome reporting. No statistical comparison was undertaken.Reliable results (high quality information) were obtained for 53 pairs of drug and dose in painful postsurgical conditions; these included various fixed dose combinations, and fast acting formulations of some analgesics. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours. Good (low) NNTs were obtained with ibuprofen 200 mg plus paracetamol (acetaminophen) 500 mg (NNT compared with placebo 1.6; 95% confidence interval 1.5 to 1.8), ibuprofen fast acting 200 mg (2.1; 1.9 to 2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9 to 3.1), diclofenac potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg (1.8; 1.7 to 2.0). For comparison, ibuprofen acid 400 mg had an NNT of 2.5 (2.4 to 2.6). Not all participants had good pain relief and, for many pairs of drug and dose, 50% or more did not achieve at least 50% maximum pain relief over four to six hours.Long duration of action (eight hours or greater) was found for etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg, naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000 mg.There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500 mg, and oxycodone 5 mg (low quality evidence). No trial data were available in reviews of acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for nine drugs and doses, and data potentially susceptible to publication bias for 13 drugs and doses (very low quality evidence).
AUTHORS' CONCLUSIONS
There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can produce good and often long-lasting analgesia at relatively low doses. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.
Topics: Acute Pain; Administration, Oral; Adult; Analgesics; Humans; Pain, Postoperative
PubMed: 26414123
DOI: 10.1002/14651858.CD008659.pub3 -
BMJ Clinical Evidence Feb 2011Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections,... (Review)
Review
INTRODUCTION
Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to a third of adults are carriers of the defective sickle cell gene, and 1% to 2% of babies are born with the disease.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: what are the effects of pharmaceutical and non-pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? What are the effects of pharmaceutical and non-pharmaceutical interventions to treat pain in people with sickle cell crisis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 38 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, antibiotic prophylaxis in children <5 years of age, antibiotic prophylaxis in childrenĀ >5 years of age, aspirin, avoidance of cold environment, blood transfusion, codeine, corticosteroid (with narcotic analgesics), diflunisal, hydration, hydroxyurea, ibuprofen, ketorolac, limiting physical exercise, malaria chemoprophylaxis, morphine (controlled-release oral after initial intravenous bolus, repeated intravenous doses), oxygen, paracetamol, patient-controlled analgesia, pneumococcal vaccines, and rehydration.
Topics: Acute Disease; Analgesia, Patient-Controlled; Anemia, Sickle Cell; Blood Transfusion; Humans; Hydroxyurea; Pneumococcal Vaccines
PubMed: 21718552
DOI: No ID Found -
Acta Neurologica Scandinavica Feb 2019Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive disorder,...
Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive disorder, predominantly manifesting as length-dependent, small fiber dominant, axonal polyneuropathy and frequently associated with cardiac disorders and other multisystem diseases. ATTRm amyloidosis is due to variants in the TTR gene, with the substitution Val30Met as the most frequent mutation. TTR mutations lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, and formation of amyloid fibrils, which are consecutively deposited extracellularly in various tissues, such as nerves, heart, brain, eyes, intestines, kidneys, or the skin. Neuropathy may not only include large nerve fibers but also small fibers, and not only sensory and motor fibers but also autonomic fibers. Types of TTR variants, age at onset, penetrance, and clinical presentation vary between geographical areas. Suggestive of a ATTRm amyloidosis are a sensorimotor polyneuropathy, positive family history, autonomic dysfunction, cardiomyopathy, carpal tunnel syndrome, unexplained weight loss, and resistance to immunotherapy. If only sensory A-delta or C fibers are affected, small fiber neuropathy ensues. Diagnostic tests for small fiber neuropathy include determination of intraepidermal nerve fiber density, laser-evoked potentials, heat- and cold-detection thresholds, and measurement of the electrochemical skin conductance. Therapy currently relies on liver transplantation and TTR-stabilizers (tafamidis, diflunisal).
Topics: Amyloid Neuropathies, Familial; Humans; Mutation; Prealbumin
PubMed: 30295933
DOI: 10.1111/ane.13035 -
BMJ Clinical Evidence Mar 2009Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises, and increases the risk of stroke, organ damage, bacterial infections, and... (Review)
Review
INTRODUCTION
Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises, and increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to a third of adults are carriers of the defective sickle cell gene, and 1-2% of babies are born with the disease.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmaceutical and non-pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? What are the effects of pharmaceutical and non-pharmaceutical interventions to treat pain in people with sickle cell crisis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 38 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, antibiotic prophylaxis in children under 5 years of age, aspirin, avoidance of cold environment, blood transfusion, codeine, corticosteroid (with narcotic analgesics), diflunisal, hydration, hydroxyurea, ibuprofen, ketorolac, limiting physical exercise, malaria chemoprophylaxis, morphine (controlled-release oral after initial intravenous bolus, repeated intravenous doses), oxygen, paracetamol, patient-controlled analgesia, penicillin prophylaxis in children over 5 years of age, piracetam, pneumococcal vaccines, rehydration, and zinc sulphate.
Topics: Acute Disease; Analgesia, Patient-Controlled; Anemia, Sickle Cell; Blood Transfusion; Humans; Malaria; Pneumococcal Vaccines
PubMed: 19445751
DOI: No ID Found -
Heart Failure Reviews Mar 2022Transthyretin cardiac amyloidosis (ATTR-CM) is caused by the accumulation of misfolded transthyretin (TTR) protein in the myocardium. Diflunisal, an agent that... (Review)
Review
Transthyretin cardiac amyloidosis (ATTR-CM) is caused by the accumulation of misfolded transthyretin (TTR) protein in the myocardium. Diflunisal, an agent that stabilizes TTR, has been used as an off-label therapeutic for ATTR-CM. Given limited data surrounding the use of diflunisal, a systematic review of the literature is warranted. We searched the PubMed, MEDLINE, and Embase databases for studies that reported on the use of diflunisal therapy for patients with ATTR-CM. We included English language studies which assessed the effect of diflunisal in adult patients with ATTR-CM who received diflunisal as primary treatment and reported clinical outcomes with emphasis on studies that noted the safety and efficacy of diflunisal in cardiac manifestations of ATTR amyloidosis. We excluded studies which did not use diflunisal therapy or used diflunisal therapy for non-cardiac manifestations of TTR amyloidosis. We also excluded case reports, abstracts, oral presentations, and studies with fewer than 10 subjects. Our search yielded 316 records, and we included 6 studies reporting on 400 patients. Non-comparative single-arm small non-randomized trials for diflunisal comprised 4 of the included studies. The 2 studies that compared diflunisal versus no treatment found improvements in TTR concentration, left atrial volume index, cardiac troponin I, and global longitudinal strain. Overall, diflunisal use was associated with decreased mortality and number of orthotopic heart transplant in ATTR-CM patients. Although a smaller number of patients had to stop treatment due to gastrointestinal side effects and transient renal dysfunction, there were no severe reactions reported in the studies included in our review. This systematic review supports the use of diflunisal for ATTR-CM. Additional long-term analyses and randomized clinical trials are needed to confirm these results.
Topics: Adult; Amyloid Neuropathies, Familial; Diflunisal; Humans; Myocardium; Prealbumin
PubMed: 34272629
DOI: 10.1007/s10741-021-10143-4 -
Journal of the American Heart... Oct 2020Background The emergence of specific therapies for transthyretin cardiac amyloidosis (CA) warrants the need for a systematic review of the literature. Methods and...
Background The emergence of specific therapies for transthyretin cardiac amyloidosis (CA) warrants the need for a systematic review of the literature. Methods and Results A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was performed on MEDLINE, PubMed, and Embase databases on November 29, 2019. Studies were selected based on the following predefined eligibility criteria: English-language randomized controlled trials (RCTs), non-RCTs, or observational studies, which included adult patients with variant/wild-type transthyretin-CA, assessed specific therapies for transthyretin-CA, and reported cardiovascular outcomes. Relevant data were extracted to a predefined template. Quality assessment was based on National Institute for Health and Care Excellence recommendations (RCTs) or a checklist by Downs and Black (non-RCTs). From 1203 records, 24 publications were selected, describing 4 RCTs (6 publications) and 16 non-RCTs (18 publications). Tafamidis was shown to significantly improve all-cause mortality and cardiovascular hospitalizations and reduce worsening in 6-minute walk test, Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in variant/wild-type transthyretin-CA. Patisiran showed promising results in a subgroup analysis of patients with variant transthyretin-CA, which have to be confirmed in RCTs. Inotersen showed conflicting results on cardiac imaging parameters. The one study on AG10 had only a 1-month duration and cardiovascular end points were exploratory and limited to cardiac biomarkers. Limited evidence from noncomparative single-arm small non-RCTs existed for diflunisal, epigallocatechin-3-gallate (green tea extract), and doxycycline+tauroursodeoxycholic acid/ursodeoxycholic acid. Conclusions This systematic review of the literature supports the use of tafamidis in wild-type and variant transthyretin-CA. Novel therapeutic targets including transthyretin gene silencers are currently under investigation.
Topics: Amyloid Neuropathies, Familial; Benzoxazoles; Cardiomyopathies; Cardiovascular Agents; Genetic Therapy; Humans
PubMed: 32969287
DOI: 10.1161/JAHA.120.016614 -
Otolaryngology--head and Neck Surgery :... Mar 2015To perform a systematic review evaluating the association between sensorineural hearing loss and (1) nonsteroidal anti-inflammatory drugs (NSAIDs) as a class, (2) NSAIDs... (Review)
Review
OBJECTIVE
To perform a systematic review evaluating the association between sensorineural hearing loss and (1) nonsteroidal anti-inflammatory drugs (NSAIDs) as a class, (2) NSAIDs available over the counter, (3) NSAIDs in short intravenous courses, (4) prescription NSAIDs utilized by patients without systemic inflammatory conditions, (5) prescription NSAIDs in patients with arthritides, and (6) acetaminophen with and without concomitant narcotic usage.
DATA SOURCES
Computerized searches of PubMed, EMBASE, and the Cochrane Library were updated through May 2014, along with manual searches and inquiries to topic experts.
REVIEW METHODS
The systematic review was performed according to an a priori protocol. Data extraction was performed by 2 independent investigators, and it focused on relevant audiologic measurements, methodological elements related to risk of bias, and potential confounders.
RESULTS
The 23 criterion-meeting studies included a total of 92,532 participants, with mixed results. Sulindac was the only specific agent to have been studied with formal audiometry in a randomized double-blind placebo-controlled trial in which hearing was the reported primary outcome: Although an effect was seen in the unadjusted analysis (pure tone threshold>15 dB, 9.3% vs 2.9%; relative risk [RR], 3.2; confidence interval [CI], 1.09-9.55; P=.02), the effect dissipated in the adjusted analysis (P=.09). There was a significant effect on self-reported hearing loss from NSAIDs as a class (RR, 1.21; CI, 1.11-1.33), ibuprofen (RR, 1.13; CI, 1.06-1.19), and acetaminophen (RR, 1.21; CI, 1.11-1.33), but no formal audiometric data confirm or refute this suggested effect. Audiometry has demonstrated profound loss in some instances of acetaminophen-narcotic combination ingestions.
CONCLUSIONS
Data are varied regarding the impact of NSAIDs and acetaminophen on population hearing health.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Audiometry; Hearing; Hearing Loss, Sensorineural; Humans; Risk Factors
PubMed: 25560405
DOI: 10.1177/0194599814564533 -
The Cochrane Database of Systematic... 2004Patellofemoral pain syndrome (PFPS) is common among adolescents and young adults. It is characterised by pain behind or around the patella and crepitations, provoked by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patellofemoral pain syndrome (PFPS) is common among adolescents and young adults. It is characterised by pain behind or around the patella and crepitations, provoked by ascending or descending stairs, squatting, prolonged sitting with flexed knees, running and cycling. The symptoms impede function in daily activities or sports. Pharmacological treatments focus on reducing pain symptoms (non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticosteroids), or restoring the assumed underlying pathology (compounds containing glucosamine to stimulate cartilage metabolism, anabolic steroids to increase bone density of the patella and build up supporting muscles). In studies, drugs are usually applied in addition to exercises aimed at building up supporting musculature.
OBJECTIVES
This review aims to summarise the evidence of effectiveness of pharmacotherapy in reducing anterior knee pain and improving knee function in people with PFPS.
SEARCH STRATEGY
We searched the Cochrane Musculoskeletal Injuries Group and Cochrane Rehabilitation and Related Therapies Field trials registers, the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2003), PEDro (up to January 2004), MEDLINE (1966 to January 2004), EMBASE (1988 to January 2004), and CINAHL (1982 to January 2004).
SELECTION CRITERIA
Controlled trials (randomised or not) comparing pharmacotherapy with placebo, different types of pharmacotherapy, or pharmacotherapy to other therapies for people with PFPS.
DATA COLLECTION AND ANALYSIS
The literature search yielded 780 publications. Eight trials were included, of which three were of high quality. Data were analysed qualitatively using best evidence synthesis, because meta-analysis was impeded by differences in route of administration of drugs, care programs and outcome measures.
MAIN RESULTS
Four trials (163 participants) studied the effect of NSAIDs. Aspirin compared to placebo in a high quality trial produced no significant differences in clinical symptoms and signs. Naproxen produced significant short term pain reduction when compared to placebo, but not when compared to diflunisal. Laser therapy to stimulate blood flow in tender areas led to more satisfied participants than tenoxicam, though not significantly. Two high quality RCTs (84 participants) studied the effect of glycosaminoglycan polysulphate (GAGPS). Twelve intramuscular injections in six weeks led to significantly more participants with a good overall therapeutic effect after one year, and to significantly better pain reduction during one of two activities. Five weekly intra-articular injections of GAGPS and lidocaine were compared with intra-articular injections of saline and lidocaine or no injections, all with concurrent quadriceps training. Injected participants showed better function after six weeks, though only the difference between GAGPS injected participants and non-injected participants was significant. The differences had disappeared after one year. One trial (43 participants) found that intramuscular injections of the anabolic steroid nandrolone phenylpropionate significantly improved both pain and function compared to placebo injections.
REVIEWERS' CONCLUSIONS
There is only limited evidence for the effectiveness of NSAIDs for short term pain reduction in PFPS. The evidence for the effect of glycosaminoglycan polysulphate is conflicting and merits further investigation. The anabolic steroid nandrolone may be effective, but is too controversial for treatment of PFPS.
Topics: Anabolic Agents; Anti-Inflammatory Agents, Non-Steroidal; Controlled Clinical Trials as Topic; Glycosaminoglycans; Humans; Nandrolone; Patellofemoral Pain Syndrome
PubMed: 15266488
DOI: 10.1002/14651858.CD003470.pub2