-
Annals of Internal Medicine Apr 2012Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza.
PURPOSE
To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza.
DATA SOURCES
MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists.
STUDY SELECTION
Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness.
DATA EXTRACTION
Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.
DATA SYNTHESIS
74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low-quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine.
LIMITATIONS
Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias.
CONCLUSION
Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low. PRIMARY FUNDING SOURCES: World Health Organization and McMaster University.
Topics: Administration, Inhalation; Administration, Oral; Amantadine; Antiviral Agents; Confounding Factors, Epidemiologic; Hospitalization; Humans; Influenza, Human; Oseltamivir; Rimantadine; Treatment Outcome; Zanamivir
PubMed: 22371849
DOI: 10.7326/0003-4819-156-7-201204030-00411 -
Journal of Comparative Effectiveness... Aug 2022To assess the clinical efficacy and safety profile of opicapone (25 and 50 mg once daily) versus placebo. Levodopa-treated adults with Parkinson's disease. A... (Meta-Analysis)
Meta-Analysis Review
To assess the clinical efficacy and safety profile of opicapone (25 and 50 mg once daily) versus placebo. Levodopa-treated adults with Parkinson's disease. A systematic review and meta-analysis were conducted. Opicapone provided a greater reduction in the absolute OFF-time, increased the chances of ≥1-h reduction in the OFF-time and ≥1-h increase in the ON-time compared with placebo. Receiving opicapone more often facilitated levodopa dose reduction versus placebo. There were no differences in the occurrence of adverse events (severe and leading to drug discontinuation), but receiving opicapone increased the frequency of dyskinesia. Opicapone demonstrated superior clinical efficacy to placebo, with a comparable general safety profile.
Topics: Adult; Antiparkinson Agents; Catechol O-Methyltransferase Inhibitors; Double-Blind Method; Humans; Levodopa; Oxadiazoles; Parkinson Disease
PubMed: 35758044
DOI: 10.2217/cer-2022-0031 -
The Cochrane Database of Systematic... Oct 2015People with Down syndrome are vulnerable to developing dementia at an earlier age than the general population. Alzheimer's disease and cognitive decline in people with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with Down syndrome are vulnerable to developing dementia at an earlier age than the general population. Alzheimer's disease and cognitive decline in people with Down syndrome can place a significant burden on both the person with Down syndrome and their family and carers. Various pharmacological interventions, including donepezil, galantamine, memantine and rivastigmine, appear to have some effect in treating cognitive decline in people without Down syndrome, but their effectiveness for those with Down syndrome remains unclear.
OBJECTIVES
To assess the effectiveness of anti-dementia pharmacological interventions and nutritional supplements for treating cognitive decline in people with Down syndrome.
SEARCH METHODS
In January 2015, we searched CENTRAL, ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), Ovid MEDLINE, Embase, PsycINFO, seven other databases, and two trials registers. In addition, we checked the references of relevant reviews and studies and contacted study authors, other researchers and relevant drug manufacturers to identify additional studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of anti-dementia pharmacological interventions or nutritional supplements for adults (aged 18 years and older) with Down syndrome, in which treatment was administered and compared with either placebo or no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the risk of bias of included trials and extracted the relevant data. Review authors contacted study authors to obtain missing information where necessary.
MAIN RESULTS
Only nine studies (427 participants) met the inclusion criteria for this review. Four of these (192 participants) assessed the effectiveness of donepezil, two (139 participants) assessed memantine, one (21 participants) assessed simvastatin, one study (35 participants) assessed antioxidants, and one study (40 participants) assessed acetyl-L-carnitine.Five studies focused on adults aged 45 to 55 years, while the remaining four studies focused on adults aged 20 to 29 years. Seven studies were conducted in either the USA or UK, one between Norway and the UK, and one in Japan. Follow-up periods in studies ranged from four weeks to two years. The reviewers judged all included studies to be at low or unclear risk of bias.Analyses indicate that for participants who received donepezil, scores in measures of cognitive functioning (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) -0.27 to 1.13) and measures of behaviour (SMD 0.42, 95% CI -0.06 to 0.89) were similar to those who received placebo. However, participants who received donepezil were significantly more likely to experience an adverse event (odds ratio (OR) 0.32, 95% CI 0.16 to 0.62). The quality of this body of evidence was low. None of the included donepezil studies reported data for carer stress, institutional/home care, or death.For participants who received memantine, scores in measures of cognitive functioning (SMD 0.05, 95% CI -0.43 to 0.52), behaviour (SMD -0.17, 95% CI -0.46 to 0.11), and occurrence of adverse events (OR 0.45, 95% CI 0.18 to 1.17) were similar to those who received placebo. The quality of this body of evidence was low. None of the included memantine studies reported data for carer stress, institutional/home care, or death.Due to insufficient data, it was possible to provide a narrative account only of the outcomes for simvastatin, antioxidants, and acetyl-L-carnitine. Results from one pilot study suggest that participants who received simvastatin may have shown a slight improvement in cognitive measures.
AUTHORS' CONCLUSIONS
Due to the low quality of the body of evidence in this review, it is difficult to draw conclusions about the effectiveness of any pharmacological intervention for cognitive decline in people with Down syndrome.
Topics: Acetylcarnitine; Adult; Antioxidants; Cognition; Cognition Disorders; Donepezil; Down Syndrome; Humans; Indans; Memantine; Middle Aged; Nootropic Agents; Piperidines; Randomized Controlled Trials as Topic; Simvastatin
PubMed: 26513128
DOI: 10.1002/14651858.CD011546.pub2 -
The Cochrane Database of Systematic... Nov 2012Psychotropic drugs are associated with sexual dysfunction. Symptoms may concern penile erection, lubrication, orgasm, libido, retrograde ejaculation, sexual arousal, or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psychotropic drugs are associated with sexual dysfunction. Symptoms may concern penile erection, lubrication, orgasm, libido, retrograde ejaculation, sexual arousal, or overall sexual satisfaction. These are major aspects of tolerability and can highly affect patients' compliance.
OBJECTIVES
To determine the effects of different strategies (e.g. dose reduction, drug holidays, adjunctive medication, switching to another drug) for treatment of sexual dysfunction due to antipsychotic therapy.
SEARCH METHODS
An updated search was performed in the Cochrane Schizophrenia Group's Trials Register (3 May 2012) and the references of all identified studies for further trials.
SELECTION CRITERIA
We included all relevant randomised controlled trials involving people with schizophrenia and sexual dysfunction.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data we calculated random effects risk ratios (RR) with 95% confidence intervals (CI), for crossover trials we calculated Odds Ratios (OR) with 95% CI. For continuous data, we calculated mean differences (MD) on the basis of a random-effects model. We analysed cross-over trials under consideration of correlation of paired measures.
MAIN RESULTS
Currently this review includes four pioneering studies (total n = 138 , duration two weeks to four months), two of which are cross-over trials. One trial reported significantly more erections sufficient for penetration when receiving sildenafil compared with when receiving placebo (n = 32, MD 3.20 95% CI 1.83 to 4.57), a greater mean duration of erections (n = 32, MD 1.18 95% CI 0.52 to 1.84) and frequency of satisfactory intercourse (n = 32, MD 2.84 95% CI 1.61 to 4.07). The second trial found no evidence for selegiline as symptomatic treatment for antipsychotic-induced sexual dysfunction compared with placebo (n = 10, MD change on Aizenberg's sexual functioning scale -0.40 95% CI -3.95 to 3.15). No evidence was found for switching to quetiapine from risperidone to improve sexual functioning (n = 36, MD -2.02 95% CI -5.79 to 1.75). One trial reported significant improvement in sexual functioning when participants switched from risperidone or an typical antipsychotic to olanzapine (n = 54, MD -0.80 95% CI -1.55 to -0.05).
AUTHORS' CONCLUSIONS
We are not confident that cross-over studies are appropriate for this participant group as they are best for conditions that are stable and for interventions with no physiological and psychological carry-over. Sildenafil may be a useful option in the treatment of antipsychotic-induced sexual dysfunction in men with schizophrenia, but this conclusion is based only on one small short trial. Switching to olanzapine may improve sexual functioning in men and women, but the trial assessing this was a small, open label trial. Further well designed randomised control trials that are blinded and well conducted and reported, which investigate the effects of dose reduction, drug holidays, symptomatic therapy and switching antipsychotic on sexual function in people with antipsychotic-induced sexual dysfunction are urgently needed.
Topics: Antipsychotic Agents; Benzodiazepines; Cross-Over Studies; Drug Substitution; Erectile Dysfunction; Female; Humans; Male; Olanzapine; Piperazines; Purines; Randomized Controlled Trials as Topic; Selegiline; Sexual Dysfunction, Physiological; Sildenafil Citrate; Sulfones; Vasodilator Agents
PubMed: 23152218
DOI: 10.1002/14651858.CD003546.pub3 -
American Journal of Alzheimer's Disease... Mar 2014The objective of this review is to summarize the current data on the pharmacological treatments for frontotemporal dementias from randomized controlled trials. A... (Review)
Review
The objective of this review is to summarize the current data on the pharmacological treatments for frontotemporal dementias from randomized controlled trials. A systematic search of 4 major databases, PubMed, Medline, PsychINFO and Cochrane, found a total of 9 randomized controlled, double-blinded clinical trials. Of these, 2 trials used the selective serotonin reuptake inhibitor (SSRI), paroxetine; 1 trial used trazodone; 2 trials used stimulants (methylphenidate and dextroamphetamine); 1 trial used the acetylcholinesterase inhibitor, galantamine; 2 trials used the N-methyl-d-aspartate antagonist, memantine; and 1 trial used the neuropeptide oxytocin. The analysis of the available data indicates that SSRIs, trazodone, and the amphetamines may be effective in reducing some behavioral symptoms, but none of these medications had an impact on cognition. Available data indicate that these medications were well tolerated in all the trials.
Topics: Cognition; Dopamine Agents; Frontotemporal Dementia; Humans; Memantine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 24164931
DOI: 10.1177/1533317513507375 -
Sleep Aug 2012A systematic literature review and meta-analyses (where appropriate) were performed to update the previous AASM practice parameters on the treatments, both dopaminergic... (Meta-Analysis)
Meta-Analysis Review
The treatment of restless legs syndrome and periodic limb movement disorder in adults--an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline.
A systematic literature review and meta-analyses (where appropriate) were performed to update the previous AASM practice parameters on the treatments, both dopaminergic and other, of RLS and PLMD. A considerable amount of literature has been published since these previous reviews were performed, necessitating an update of the corresponding practice parameters. Therapies with a STANDARD level of recommendation include pramipexole and ropinirole. Therapies with a GUIDELINE level of recommendation include levodopa with dopa decarboxylase inhibitor, opioids, gabapentin enacarbil, and cabergoline (which has additional caveats for use). Therapies with an OPTION level of recommendation include carbamazepine, gabapentin, pregabalin, clonidine, and for patients with low ferritin levels, iron supplementation. The committee recommends a STANDARD AGAINST the use of pergolide because of the risks of heart valve damage. Therapies for RLS secondary to ESRD, neuropathy, and superficial venous insufficiency are discussed. Lastly, therapies for PLMD are reviewed. However, it should be mentioned that because PLMD therapy typically mimics RLS therapy, the primary focus of this review is therapy for idiopathic RLS.
Topics: Academies and Institutes; Benzothiazoles; Cabergoline; Carbamates; Dopamine Agents; Ergolines; Evidence-Based Medicine; Humans; Indoles; Levodopa; Nocturnal Myoclonus Syndrome; Pergolide; Peripheral Nervous System Diseases; Pramipexole; Restless Legs Syndrome; Sleep Medicine Specialty; United States; Venous Insufficiency; gamma-Aminobutyric Acid
PubMed: 22851801
DOI: 10.5665/sleep.1988 -
The Cochrane Database of Systematic... Apr 2018Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist drugs, which have intense... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist drugs, which have intense sedative properties and may exacerbate psychotic symptoms, have been used to treat TD.
OBJECTIVES
1. Primary objectiveThe primary objective was to determine whether using non-benzodiazepine GABA agonist drugs for at least six weeks was clinically effective for the treatment of antipsychotic-induced TD in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses.2. Secondary objectivesThe secondary objectives were as follows.To examine whether any improvement occurred with short periods of intervention (less than six weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.To examine whether there was a differential effect between the various compounds.To test the hypothesis that GABA agonist drugs are most effective for a younger age group (less than 40 years old).
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (last searched April 2017), inspected references of all identified studies for further trials, and, when necessary, contacted authors of trials for additional information.
SELECTION CRITERIA
We included randomised controlled trials of non-benzodiazepine GABA agonist drugs in people with antipsychotic-induced TD and schizophrenia or other chronic mental illness.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected and critically appraised studies, extracted and analysed data on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous data we calculated mean differences (MD). We assumed that people who left early had no improvement. We contacted investigators to obtain missing information. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
We included 11 studies that randomised 343 people. Overall, the risk of bias in the included studies was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, participants and outcome assessors were not clearly blinded. For some studies we were unsure if data were complete, and data were often poorly or selectively reported.Data from six trials showed that there may be a clinically important improvement in TD symptoms after GABA agonist treatment compared with placebo at six to eight weeks follow-up (6 RCTs, n = 258, RR 0.83, CI 0.74 to 0.92; low-quality evidence). Data from five studies showed no difference between GABA agonist treatment and placebo for deterioration of TD symptoms (5 RCTs, n = 136, RR 1.90, CI 0.70 to 5.16; very low-quality evidence). Studies reporting adverse events found a significant effect favouring placebo compared with baclofen, sodium valproate or progabide for dizziness/confusion (3 RCTs, n = 62 RR 4.54, CI 1.14 to 18.11; very low-quality evidence) and sedation/drowsiness (4 RCTS, n = 144, RR 2.29, CI 1.08 to 4.86; very low-quality evidence). Studies reporting on akathisia (RR 1.05, CI 0.32 to 3.49, 2 RCTs, 80 participants), ataxia (RR 3.25, CI 0.36 to 29.73, 2 RCTs, 95 participants), nausea/vomiting (RR 2.61, CI 0.79 to 8.67, 2 RCTs, 64 participants), loss of muscle tone (RR 3.00, CI 0.15 to 59.89, 1 RCT, 10 participants), seizures (RR 3.00, CI 0.24 to 37.67, 1 RCT, 2 participants), hypotension (RR 3.04, CI 0.33 to 28.31, 2 RCTs, 119 participants) found no significant difference between GABA drug and placebo (very low-quality evidence). Evidence on mental state also showed no effect between treatment groups (6 RCTS, n = 121, RR 2.65, CI 0.71 to 9.86; very low-quality evidence) as did data for leaving the study early (around 10% in both groups, 6 RCTS, n = 218, RR 1.47, CI 0.69 to 3.15; very low-quality evidence). No study reported on social confidence, social inclusion, social networks, or personalised quality of life, a group of outcomes selected as being of particular importance to patients.
AUTHORS' CONCLUSIONS
We are uncertain about the evidence of the effects of baclofen, progabide, sodium valproate or tetrahydroisoxazolopyridinol (THIP) for people with antipsychotic-induced TD. Evidence is inconclusive and unconvincing. The quality of data available for main outcomes ranges from very low to low. Any possible benefits are likely to be outweighed by the adverse effects associated with their use.
Topics: Antipsychotic Agents; Baclofen; Dyskinesia, Drug-Induced; GABA Agonists; Humans; Isoxazoles; Placebos; Randomized Controlled Trials as Topic; Valproic Acid; gamma-Aminobutyric Acid
PubMed: 29663328
DOI: 10.1002/14651858.CD000203.pub4 -
The Cochrane Database of Systematic... 2001Long term levodopa therapy in Parkinson's disease is associated with the development of motor complications including abnormal involuntary movements and a shortening... (Review)
Review
BACKGROUND
Long term levodopa therapy in Parkinson's disease is associated with the development of motor complications including abnormal involuntary movements and a shortening response to each dose (wearing off phenomenon). It is thought that dopamine agonists can reduce the duration of immobile off periods and the need for levodopa therapy whilst maintaining or improving motor impairments and only minimally increasing dopaminergic adverse events.
OBJECTIVES
To compare the efficacy and safety of adjuvant cabergoline therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.
SEARCH STRATEGY
Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Pharmacia Upjohn Limited.
SELECTION CRITERIA
Randomised controlled trials of cabergoline versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.
DATA COLLECTION AND ANALYSIS
Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, off time measurements and the frequency of withdrawals and adverse events.
MAIN RESULTS
Cabergoline has been compared with bromocriptine in five randomised, double-blind, parallel group studies including 1071 patients. Only one of the phase II studies was medium term (36 weeks), the others all being short term (12 -15 weeks). The non-significant difference in off time reduction produced by cabergoline compared with bromocriptine was 0.29 hours/day in favour of the former (weighted mean difference; 95% CI -0.10, 0.68; p = 0.15). Dyskinesia reported as an adverse event was significantly increased with cabergoline compared with bromocriptine (Peto odds ratio 1.57; 95% CI 1.05, 2.35; p = 0.03). Motor impairment and disability were measured in four of the studies using the UPDRS rating scale but the small differences in UPDRS ADL (part II) and motor (part III) scores were not statistically significant in any study. Similarly, no significant difference in Schwab and England score was seen. The number of patients rated as much or very much improved on a clinician's global impression scale was similar with both agonists. Levodopa dose reduction was no different between cabergoline and bromocriptine. There was more confusion with cabergoline (Peto odds ratio 2.02; 95% CI 1.09, 3.76; p = 0.03). Otherwise, dopaminergic adverse events were comparable with these agonists and no significant difference in all cause withdrawal rate was found.
REVIEWER'S CONCLUSIONS
Cabergoline produces similar benefits to bromocriptine in off time reduction, motor impairment and disability ratings, and levodopa dose reduction over the first three months of therapy. Dyskinesia and confusion were increased with cabergoline but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two agonists.
Topics: Antiparkinson Agents; Bromocriptine; Cabergoline; Dopamine Agonists; Dyskinesia, Drug-Induced; Ergolines; Humans; Levodopa; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 11279721
DOI: 10.1002/14651858.CD001519 -
Health Technology Assessment... Feb 2009To evaluate the clinical effectiveness and incremental cost-effectiveness of amantadine, oseltamivir and zanamivir for seasonal and post-exposure prophylaxis of... (Review)
Review
OBJECTIVES
To evaluate the clinical effectiveness and incremental cost-effectiveness of amantadine, oseltamivir and zanamivir for seasonal and post-exposure prophylaxis of influenza.
DATA SOURCES
A MEDLINE search strategy was used and searches were carried out in July 2007.
REVIEW METHODS
An independent health economic model was developed based on a review of existing cost-effectiveness models and clinical advice.The model draws together a broad spectrum of evidence relating to the costs and consequences associated with influenza and its prevention. Where direct evidence concerning the effectiveness of prophylaxis within specific model subgroups was lacking, the model uses estimates from mixed subgroups or extrapolates from other mutually exclusive subgroups.
RESULTS
Twenty-six published references relating to 22 randomised controlled trials (RCTs) were included in the clinical effectiveness review, along with one unpublished report. Eight, six and nine RCTs were included for amantadine, oseltamivir and zanamivir respectively. The study quality was variable and gaps in the evidence base limited the assessment of the clinical effectiveness of the interventions. For seasonal prophylaxis, there was limited evidence for the efficacy of amantadine in preventing symptomatic, laboratory-confirmed influenza (SLCI) in healthy adults [relative risk (RR) 0.40, 95% confidence interval (CI) 0.08-2.03]. Oseltamivir was effective in preventing SLCI, particularly when used in at-risk elderly subjects (RR 0.08, 95% CI 0.01-0.63). The preventative efficacy of zanamivir was most notable in at-risk adults and adolescents (RR 0.17, 95% CI 0.07-0.44), and healthy and at-risk elderly subjects (RR 0.20, 95% CI 0.02-1.72). For post-exposure prophylaxis, data on the use of amantadine were again limited: in adolescents an RR of 0.10 (95% CI 0.03-0.34) was reported for the prevention of SLCI. Oseltamivir was effective in households of mixed composition (RR 0.19, 95% CI 0.08-0.45). The efficacy of zanamivir in post-exposure prophylaxis within households was also reported (RR 0.21, 95% CI 0.13-0.33). Interventions appeared to be well tolerated. Limited evidence was available for the effectiveness of the interventions in preventing complications and hospitalisation and in minimising length of illness and time to return to normal activities. No clinical effectiveness data were identified for health-related quality of life or mortality outcomes. With the exception of at-risk children, the incremental cost-utility of seasonal influenza prophylaxis is expected to be in the range 38,000-428,000 pounds per QALY gained (depending on subgroup). The cost-effectiveness ratios for oseltamivir and zanamivir as post-exposure prophylaxis are expected to be below 30,000 pounds per QALY gained in healthy children, at-risk children, healthy elderly and at-risk elderly individuals. Despite favourable clinical efficacy estimates, the incorporation of recent evidence of viral resistance to amantadine led to it being dominated in every economic comparison.
CONCLUSIONS
All three interventions showed some efficacy for seasonal and post-exposure prophylaxis. However, weaknesses and gaps in the clinical evidence base are directly relevant to the interpretation of the health economic model and rendered the use of advanced statistical analyses inappropriate. These data limitations should be borne in mind in interpreting the findings of the review.
Topics: Amantadine; Antiviral Agents; Cost-Benefit Analysis; Humans; Influenza, Human; Models, Economic; Oseltamivir; Practice Guidelines as Topic; Premedication; Randomized Controlled Trials as Topic; Seasons; Treatment Outcome; Zanamivir
PubMed: 19215705
DOI: 10.3310/hta13110 -
The Cochrane Database of Systematic... Oct 2004As Parkinson's disease progresses the control of the symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
As Parkinson's disease progresses the control of the symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of the levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase.
OBJECTIVES
To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus active comparators in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.
SEARCH STRATEGY
Electronic searches of the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted.
SELECTION CRITERIA
Randomised controlled trials of adjuvant COMT inhibitor therapy versus an active comparator in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.
DATA COLLECTION AND ANALYSIS
Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events.
MAIN RESULTS
Two trials were found that examined the efficacy of a COMT inhibitor against an active comparator (n = 349). Koller 1998 compared the efficacy of tolcapone versus pergolide (n = 203) over 12 weeks and TSG 1999 compared the efficacy of tolcapone versus bromocriptine (n = 146) over 8 weeks. No trials were found that compared entacapone with active comparators. Tolcapone produced similar benefits to bromocriptine in 'off' time reduction, motor impairment and disability ratings over three months of therapy. Tolcapone produced a greater reduction in levodopa dosage than bromocriptine. Tolcapone produced similar benefits to pergolide in levodopa dose reduction, motor impairment and disability ratings, and in generic health-related quality of life scales over the first two months of therapy. Tolcapone produced a greater improvement in the disease-specific quality of life scale PDQ-39 than pergolide. Nausea, constipation and orthostatic complaints were greater with agonist therapy, but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two classes of adjuvant medication. One patient had significantly elevated liver enzymes whilst on tolcapone, but otherwise the frequency of adverse events and withdrawals from treatment were similar.
REVIEWERS' CONCLUSIONS
The two trials comparing tolcapone with the dopamine agonists bromocriptine and pergolide were underpowered to detect clinically relevant differences between them. This is based on medium-term evidence. No evidence was found comparing entacapone with active comparators. Further larger and longer-term trials are required to compare tolcapone with entacapone and COMT inhibitor therapy with alternative adjuvant classes of drug in later Parkinson's disease such as dopamine agonists and monoamine oxidase inhibitors.
Topics: Antiparkinson Agents; Benzophenones; Bromocriptine; Catechol O-Methyltransferase Inhibitors; Dopamine Agonists; Humans; Levodopa; Nitrophenols; Parkinson Disease; Pergolide; Tolcapone
PubMed: 15495118
DOI: 10.1002/14651858.CD004553.pub2