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Journal of Pharmaceutical and... Mar 2019In recent years, there has been a very active debate about the stability of drug products especially after exceeding the expiry dates. The regulatory authorities require...
In recent years, there has been a very active debate about the stability of drug products especially after exceeding the expiry dates. The regulatory authorities require comprehensive stability data for market approval. The shelf-life obtained determines the expiry date, which is typically between 1 and 5 years and commonly set in a conservative manner. Conducting stability studies is a resource- and time-consuming matter for the pharmaceutical manufacturer. Short shelf-lives of drug products are also a challenge for managers of hospitals, nursing homes, and strategic national stockpile agencies which have to dispose of large quantities of outdated medicines every year. This conflict raises the question whether shelf-lives are often longer than the labeled one. In the past years, the FDA has launched several programs for shelf-life extension in order to defer replacement costs and to prevent drug shortages due to supply disruption. The aim of this review was to bring together the available literature of expired drug products as well as historical pharmaceutical relicts with an age of more than 80 years and to discuss the actual shelf-life with regard to the respective dosage form and the affiliation of the drug class. It seems to be reasonable for a large portion of drugs to extend the expiry dates far beyond five years.
Topics: Dosage Forms; Drug Labeling; Drug Stability; Pharmaceutical Preparations; Quality Control; Time Factors
PubMed: 30660807
DOI: 10.1016/j.jpba.2019.01.016 -
The Cochrane Database of Systematic... Mar 2021Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many...
BACKGROUND
Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many interventions are used to treat SLE with varying efficacy, risks, and benefits.
OBJECTIVES
To assess the effects of interventions for cutaneous disease in SLE.
SEARCH METHODS
We searched the following databases up to June 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, Wiley Interscience Online Library, and Biblioteca Virtual em Saude (Virtual Health Library). We updated our search in September 2020, but these results have not yet been fully incorporated.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of interventions for cutaneous disease in SLE compared with placebo, another intervention, no treatment, or different doses of the same intervention. We did not evaluate trials of cutaneous lupus in people without a diagnosis of SLE.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes were complete and partial clinical response. Secondary outcomes included reduction (or change) in number of clinical flares; and severe and minor adverse events. We used GRADE to assess the quality of evidence.
MAIN RESULTS
Sixty-one RCTs, involving 11,232 participants, reported 43 different interventions. Trials predominantly included women from outpatient clinics; the mean age range of participants was 20 to 40 years. Twenty-five studies reported baseline severity, and 22 studies included participants with moderate to severe cutaneous lupus erythematosus (CLE); duration of CLE was not well reported. Studies were conducted mainly in multi-centre settings. Most often treatment duration was 12 months. Risk of bias was highest for the domain of reporting bias, followed by performance/detection bias. We identified too few studies for meta-analysis for most comparisons. We limited this abstract to main comparisons (all administered orally) and outcomes. We did not identify clinical trials of other commonly used treatments, such as topical corticosteroids, that reported complete or partial clinical response or numbers of clinical flares. Complete clinical response Studies comparing oral hydroxychloroquine against placebo did not report complete clinical response. Chloroquine may increase complete clinical response at 12 months' follow-up compared with placebo (absence of skin lesions) (risk ratio (RR) 1.57, 95% confidence interval (CI) 0.95 to 2.61; 1 study, 24 participants; low-quality evidence). There may be little to no difference between methotrexate and chloroquine in complete clinical response (skin rash resolution) at 6 months' follow-up (RR 1.13, 95% CI 0.84 to 1.50; 1 study, 25 participants; low-quality evidence). Methotrexate may be superior to placebo with regard to complete clinical response (absence of malar/discoid rash) at 6 months' follow-up (RR 3.57, 95% CI 1.63 to 7.84; 1 study, 41 participants; low-quality evidence). At 12 months' follow-up, there may be little to no difference between azathioprine and ciclosporin in complete clinical response (malar rash resolution) (RR 0.83, 95% CI 0.46 to 1.52; 1 study, 89 participants; low-quality evidence). Partial clinical response Partial clinical response was reported for only one key comparison: hydroxychloroquine may increase partial clinical response at 12 months compared to placebo, but the 95% CI indicates that hydroxychloroquine may make no difference or may decrease response (RR 7.00, 95% CI 0.41 to 120.16; 20 pregnant participants, 1 trial; low-quality evidence). Clinical flares Clinical flares were reported for only two key comparisons: hydroxychloroquine is probably superior to placebo at 6 months' follow-up for reducing clinical flares (RR 0.49, 95% CI 0.28 to 0.89; 1 study, 47 participants; moderate-quality evidence). At 12 months' follow-up, there may be no difference between methotrexate and placebo, but the 95% CI indicates there may be more or fewer flares with methotrexate (RR 0.77, 95% CI 0.32 to 1.83; 1 study, 86 participants; moderate-quality evidence). Adverse events Data for adverse events were limited and were inconsistently reported, but hydroxychloroquine, chloroquine, and methotrexate have well-documented adverse effects including gastrointestinal symptoms, liver problems, and retinopathy for hydroxychloroquine and chloroquine and teratogenicity during pregnancy for methotrexate.
AUTHORS' CONCLUSIONS
Evidence supports the commonly-used treatment hydroxychloroquine, and there is also evidence supporting chloroquine and methotrexate for treating cutaneous disease in SLE. Evidence is limited due to the small number of studies reporting key outcomes. Evidence for most key outcomes was low or moderate quality, meaning findings should be interpreted with caution. Head-to-head intervention trials designed to detect differences in efficacy between treatments for specific CLE subtypes are needed. Thirteen further trials are awaiting classification and have not yet been incorporated in this review; they may alter the review conclusions.
Topics: Age of Onset; Azathioprine; Bias; Biological Factors; Chloroquine; Cosmetic Techniques; Cyclosporine; Dermatologic Agents; Exanthema; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; Male; Medicine, Chinese Traditional; Methotrexate; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Skin Diseases; Symptom Flare Up
PubMed: 33687069
DOI: 10.1002/14651858.CD007478.pub2 -
The Cochrane Database of Systematic... Jan 2017Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory... (Review)
Review
BACKGROUND
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory loss. The symptoms are due to autoimmune inflammation of peripheral nerves. CIPD affects about 2 to 3 per 100,000 of the population. More than half of affected people cannot walk unaided when symptoms are at their worst. CIDP usually responds to treatments that reduce inflammation, but there is disagreement about which treatment is most effective.
OBJECTIVES
To summarise the evidence from Cochrane systematic reviews (CSRs) and non-Cochrane systematic reviews of any treatment for CIDP and to compare the effects of treatments.
METHODS
We considered all systematic reviews of randomised controlled trials (RCTs) of any treatment for any form of CIDP. We reported their primary outcomes, giving priority to change in disability after 12 months.Two overview authors independently identified published systematic reviews for inclusion and collected data. We reported the quality of evidence using GRADE criteria. Two other review authors independently checked review selection, data extraction and quality assessments.On 31 October 2016, we searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (in theCochrane Library), MEDLINE, Embase, and CINAHL Plus for systematic reviews of CIDP. We supplemented the RCTs in the existing CSRs by searching on the same date for RCTs of any treatment of CIDP (including treatment of fatigue or pain in CIDP), in the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus.
MAIN RESULTS
Five CSRs met our inclusion criteria. We identified 23 randomised trials, of which 15 had been included in these CSRs. We were unable to compare treatments as originally planned, because outcomes and outcome intervals differed. CorticosteroidsIt is uncertain whether daily oral prednisone improved impairment compared to no treatment because the quality of the evidence was very low (1 trial, 28 participants). According to moderate-quality evidence (1 trial, 41 participants), six months' treatment with high-dose monthly oral dexamethasone did not improve disability more than daily oral prednisolone. Observational studies tell us that prolonged use of corticosteroids sometimes causes serious side-effects. Plasma exchangeAccording to moderate-quality evidence (2 trials, 59 participants), twice-weekly plasma exchange produced more short-term improvement in disability than sham exchange. In the largest observational study, 3.9% of plasma exchange procedures had complications. Intravenous immunoglobulinAccording to high-quality evidence (5 trials, 269 participants), intravenous immunoglobulin (IVIg) produced more short-term improvement than placebo. Adverse events were more common with IVIg than placebo (high-quality evidence), but serious adverse events were not (moderate-quality evidence, 3 trials, 315 participants). One trial with 19 participants provided moderate-quality evidence of little or no difference in short-term improvement of impairment with plasma exchange in comparison to IVIg. There was little or no difference in short-term improvement of disability with IVIg in comparison to oral prednisolone (moderate-quality evidence; 1 trial, 29 participants) or intravenous methylprednisolone (high-quality evidence; 1 trial, 45 participants). One unpublished randomised open trial with 35 participants found little or no difference in disability after three months of IVIg compared to oral prednisone; this trial has not yet been included in a CSR. We know from observational studies that serious adverse events related to IVIg do occur. Other immunomodulatory treatmentsIt is uncertain whether the addition of azathioprine (2 mg/kg) to prednisone improved impairment in comparison to prednisone alone, as the quality of the evidence is very low (1 trial, 27 participants). Observational studies show that adverse effects truncate treatment in 10% of people.According to low-quality evidence (1 trial, 60 participants), compared to placebo, methotrexate 15 mg/kg did not allow more participants to reduce corticosteroid or IVIg doses by 20%. Serious adverse events were no more common with methotrexate than with placebo, but observational studies show that methotrexate can cause teratogenicity, abnormal liver function, and pulmonary fibrosis.According to moderate-quality evidence (2 trials, 77 participants), interferon beta-1a (IFN beta-1a) in comparison to placebo, did not allow more people to withdraw from IVIg. According to moderate-quality evidence, serious adverse events were no more common with IFN beta-1a than with placebo.We know of no other completed trials of immunosuppressant or immunomodulatory agents for CIDP. Other treatmentsWe identified no trials of treatments for fatigue or pain in CIDP. Adverse effectsNot all trials routinely collected adverse event data; when they did, the quality of evidence was variable. Adverse effects in the short, medium, and long term occur with all interventions. We are not able to make reliable comparisons of adverse events between the interventions included in CSRs.
AUTHORS' CONCLUSIONS
We cannot be certain based on available evidence whether daily oral prednisone improves impairment compared to no treatment. However, corticosteroids are commonly used, based on widespread availability, low cost, very low-quality evidence from observational studies, and clinical experience. The weakness of the evidence does not necessarily mean that corticosteroids are ineffective. High-dose monthly oral dexamethasone for six months is probably no more or less effective than daily oral prednisolone. Plasma exchange produces short-term improvement in impairment as determined by neurological examination, and probably produces short-term improvement in disability. IVIg produces more short-term improvement in disability than placebo and more adverse events, although serious side effects are probably no more common than with placebo. There is no clear difference in short-term improvement in impairment with IVIg when compared with intravenous methylprednisolone and probably no improvement when compared with either oral prednisolone or plasma exchange. According to observational studies, adverse events related to difficult venous access, use of citrate, and haemodynamic changes occur in 3% to17% of plasma exchange procedures.It is uncertain whether azathioprine is of benefit as the quality of evidence is very low. Methotrexate may not be of benefit and IFN beta-1a is probably not of benefit.We need further research to identify predictors of response to different treatments and to compare their long-term benefits, safety and cost-effectiveness. There is a need for more randomised trials of immunosuppressive and immunomodulatory agents, routes of administration, and treatments for symptoms of CIDP.
Topics: Adrenal Cortex Hormones; Azathioprine; Dexamethasone; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Interferon beta-1a; Methotrexate; Methylprednisolone; Plasma Exchange; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Prednisone; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 28084646
DOI: 10.1002/14651858.CD010369.pub2 -
The Cochrane Database of Systematic... Dec 2020The prevalence of substance use, both prescribed and non-prescribed, is increasing in many areas of the world. Substance use by women of childbearing age contributes to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of substance use, both prescribed and non-prescribed, is increasing in many areas of the world. Substance use by women of childbearing age contributes to increasing rates of neonatal abstinence syndrome (NAS). Neonatal opioid withdrawal syndrome (NOWS) is a newer term describing the subset of NAS related to opioid exposure. Non-pharmacological care is the first-line treatment for substance withdrawal in newborns. Despite the widespread use of non-pharmacological care to mitigate symptoms of NAS, there is not an established definition of, and standard for, non-pharmacological care practices in this population. Evaluation of safety and efficacy of non-pharmacological practices could provide clear guidance for clinical practice.
OBJECTIVES
To evaluate the safety and efficacy of non-pharmacological treatment of infants at risk for, or having symptoms consistent with, opioid withdrawal on the length of hospitalization and use of pharmacological treatment for symptom management. Comparison 1: in infants at risk for, or having early symptoms consistent with, opioid withdrawal, does non-pharmacological treatment reduce the length of hospitalization and use of pharmacological treatment? Comparison 2: in infants receiving pharmacological treatment for symptoms consistent with opioid withdrawal, does concurrent non-pharmacological treatment reduce duration of pharmacological treatment, maximum and cumulative doses of opioid medication, and length of hospitalization?
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 10); Ovid MEDLINE; and CINAHL on 11 October 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs), quasi-RCTs, and cluster trials.
SELECTION CRITERIA
We included trials comparing single or bundled non-pharmacological interventions to no non-pharmacological treatment or different single or bundled non-pharmacological interventions. We assessed non-pharmacological interventions independently and in combination based on sufficient similarity in population, intervention, and comparison groups studied. We categorized non-pharmacological interventions as: modifying environmental stimulation, feeding practices, and support of the mother-infant dyad. We presented non-randomized studies identified in the search process narratively.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Primary outcomes in infants at risk for, or having early symptoms consistent with, opioid withdrawal included length of hospitalization and pharmacological treatment with one or more doses of opioid or sedative medication. Primary outcomes in infants receiving opioid treatment for symptoms consistent with opioid withdrawal included length of hospitalization, length of pharmacological treatment with opioid or sedative medication, and maximum and cumulative doses of opioid medication.
MAIN RESULTS
We identified six RCTs (353 infants) in which infants at risk for, or having symptoms consistent with, opioid withdrawal participated between 1975 and 2018. We identified no RCTs in which infants receiving opioid treatment for symptoms consistent with opioid withdrawal participated. The certainty of evidence for all outcomes was very low to low. We also identified and excluded 34 non-randomized studies published between 2005 and 2018, including 29 in which infants at risk for, or having symptoms consistent with, opioid withdrawal participated and five in which infants receiving opioid treatment for symptoms consistent with opioid withdrawal participated. We identified seven preregistered interventional clinical trials that may qualify for inclusion at review update when complete. Of the six RCTs, four studies assessed modifying environmental stimulation in the form of a mechanical rocking bed, prone positioning, non-oscillating waterbed, or a low-stimulation nursery; one study assessed feeding practices (comparing 24 kcal/oz to 20 kcal/oz formula); and one study assessed support of the maternal-infant dyad (tailored breastfeeding support). There was no evidence of a difference in length of hospitalization in the one study that assessed modifying environmental stimulation (mean difference [MD) -1 day, 95% confidence interval [CI) -2.82 to 0.82; 30 infants; very low-certainty evidence) and the one study of support of the maternal-infant dyad (MD -8.9 days, 95% CI -19.84 to 2.04; 14 infants; very low-certainty evidence). No studies of feeding practices evaluated the length of hospitalization. There was no evidence of a difference in use of pharmacological treatment in three studies of modifying environmental stimulation (typical risk ratio [RR) 1.00, 95% CI 0.86 to 1.16; 92 infants; low-certainty evidence), one study of feeding practices (RR 0.92, 95% CI 0.63 to 1.33; 49 infants; very low-certainty evidence), and one study of support of the maternal-infant dyad (RR 0.50, 95% CI 0.13 to 1.90; 14 infants; very low-certainty evidence). Reported secondary outcomes included neonatal intensive care unit (NICU) admission, days to regain birth weight, and weight nadir. One study of support of the maternal-infant dyad reported NICU admission (RR 0.50, 95% CI 0.13 to 1.90; 14 infants; very low-certainty evidence). One study of feeding practices reported days to regain birth weight (MD 1.10 days, 95% CI 2.76 to 0.56; 46 infants; very low-certainty evidence). One study that assessed modifying environmental stimulation reported weight nadir (MD -0.28, 95% CI -1.15 to 0.59; 194 infants; very low-certainty evidence) and one study of feeding practices reported weight nadir (MD -0.8, 95% CI -2.24 to 0.64; 46 infants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
We are uncertain whether non-pharmacological care for opioid withdrawal in newborns affects important clinical outcomes including length of hospitalization and use of pharmacological treatment based on the six included studies. The outcomes identified for this review were of very low- to low-certainty evidence. Combined analysis was limited by heterogeneity in study design and intervention definitions as well as the number of studies. Many prespecified outcomes were not reported. Although caregivers are encouraged by experts to optimize non-pharmacological care for opioid withdrawal in newborns prior to initiating pharmacological care, we do not have sufficient evidence to inform specific clinical practices. Larger well-designed studies are needed to determine the effect of non-pharmacological care for opioid withdrawal in newborns.
Topics: Beds; Breast Feeding; Environment Design; Humans; Hypnotics and Sedatives; Infant Equipment; Infant, Newborn; Intensive Care Units, Neonatal; Length of Stay; Narcotics; Neonatal Abstinence Syndrome; Nurseries, Infant; Opiate Substitution Treatment; Patient Positioning; Prone Position; Randomized Controlled Trials as Topic
PubMed: 33348423
DOI: 10.1002/14651858.CD013217.pub2 -
The Cochrane Database of Systematic... Apr 2014Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide.
OBJECTIVES
To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments.
SEARCH METHODS
We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database.
SELECTION CRITERIA
Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza.
DATA COLLECTION AND ANALYSIS
We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers.
MAIN RESULTS
We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P < 0.0001). This represents a reduction in the time to first alleviation of symptoms from 7 to 6.3 days. There was no effect in asthmatic children, but in otherwise healthy children there was (reduction by a mean difference of 29 hours, 95% CI 12 to 47 hours, P = 0.001). Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days, P < 0.00001), equating to a reduction in the mean duration of symptoms from 6.6 to 6.0 days. The effect in children was not significant. In subgroup analysis we found no evidence of a difference in treatment effect for zanamivir on time to first alleviation of symptoms in adults in the influenza-infected and non-influenza-infected subgroups (P = 0.53). Hospitalisations. Treatment of adults with oseltamivir had no significant effect on hospitalisations: risk difference (RD) 0.15% (95% CI -0.78 to 0.91). There was also no significant effect in children or in prophylaxis. Zanamivir hospitalisation data were unreported. Serious influenza complications or those leading to study withdrawal. In adult treatment trials, oseltamivir did not significantly reduce those complications classified as serious or those which led to study withdrawal (RD 0.07%, 95% CI -0.78 to 0.44), nor in child treatment trials; neither did zanamivir in the treatment of adults or in prophylaxis. There were insufficient events to compare this outcome for oseltamivir in prophylaxis or zanamivir in the treatment of children. Pneumonia. Oseltamivir significantly reduced self reported, investigator-mediated, unverified pneumonia (RD 1.00%, 95% CI 0.22 to 1.49); number needed to treat to benefit (NNTB) = 100 (95% CI 67 to 451) in the treated population. The effect was not significant in the five trials that used a more detailed diagnostic form for pneumonia. There were no definitions of pneumonia (or other complications) in any trial. No oseltamivir treatment studies reported effects on radiologically confirmed pneumonia. There was no significant effect on unverified pneumonia in children. There was no significant effect of zanamivir on either self reported or radiologically confirmed pneumonia. In prophylaxis, zanamivir significantly reduced the risk of self reported, investigator-mediated, unverified pneumonia in adults (RD 0.32%, 95% CI 0.09 to 0.41); NNTB = 311 (95% CI 244 to 1086), but not oseltamivir. Bronchitis, sinusitis and otitis media. Zanamivir significantly reduced the risk of bronchitis in adult treatment trials (RD 1.80%, 95% CI 0.65 to 2.80); NNTB = 56 (36 to 155), but not oseltamivir. Neither NI significantly reduced the risk of otitis media and sinusitis in both adults and children. Harms of treatment. Oseltamivir in the treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90 to 7.39); number needed to treat to harm (NNTH) = 28 (95% CI 14 to 112) and vomiting (RD 4.56%, 95% CI 2.39 to 7.58); NNTH = 22 (14 to 42). The proportion of participants with four-fold increases in antibody titre was significantly lower in the treated group compared to the control group (RR 0.92, 95% CI 0.86 to 0.97, I(2) statistic = 0%) (5% absolute difference between arms). Oseltamivir significantly decreased the risk of diarrhoea (RD 2.33%, 95% CI 0.14 to 3.81); NNTB = 43 (95% CI 27 to 709) and cardiac events (RD 0.68%, 95% CI 0.04 to 1.0); NNTB = 148 (101 to 2509) compared to placebo during the on-treatment period. There was a dose-response effect on psychiatric events in the two oseltamivir "pivotal" treatment trials, WV15670 and WV15671, at 150 mg (standard dose) and 300 mg daily (high dose) (P = 0.038). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75 to 10.29); NNTH = 19 (95% CI 10 to 57). There was a significantly lower proportion of children on oseltamivir with a four-fold increase in antibodies (RR 0.90, 95% CI 0.80 to 1.00, I(2) = 0%). Prophylaxis. In prophylaxis trials, oseltamivir and zanamivir reduced the risk of symptomatic influenza in individuals (oseltamivir: RD 3.05% (95% CI 1.83 to 3.88); NNTB = 33 (26 to 55); zanamivir: RD 1.98% (95% CI 0.98 to 2.54); NNTB = 51 (40 to 103)) and in households (oseltamivir: RD 13.6% (95% CI 9.52 to 15.47); NNTB = 7 (6 to 11); zanamivir: RD 14.84% (95% CI 12.18 to 16.55); NNTB = 7 (7 to 9)). There was no significant effect on asymptomatic influenza (oseltamivir: RR 1.14 (95% CI 0.39 to 3.33); zanamivir: RR 0.97 (95% CI 0.76 to 1.24)). Non-influenza, influenza-like illness could not be assessed due to data not being fully reported. In oseltamivir prophylaxis studies, psychiatric adverse events were increased in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07 to 2.76); NNTH = 94 (95% CI 36 to 1538) in the study treatment population. Oseltamivir increased the risk of headaches whilst on treatment (RD 3.15%, 95% CI 0.88 to 5.78); NNTH = 32 (95% CI 18 to 115), renal events whilst on treatment (RD 0.67%, 95% CI -2.93 to 0.01); NNTH = 150 (NNTH 35 to NNTB > 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116).
AUTHORS' CONCLUSIONS
Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence.
Topics: Adult; Antiviral Agents; Child; Drug Evaluation; Enzyme Inhibitors; Europe; Health Status; Humans; Influenza, Human; Japan; Legislation, Drug; Neuraminidase; Oseltamivir; Pneumonia; Publication Bias; Randomized Controlled Trials as Topic; United Kingdom; United States; Zanamivir
PubMed: 24718923
DOI: 10.1002/14651858.CD008965.pub4 -
The Cochrane Database of Systematic... Mar 2020Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease, which is the more prevalent form of dry eye disease. Intense pulsed light (IPL)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease, which is the more prevalent form of dry eye disease. Intense pulsed light (IPL) therapy, involving treatment of the skin near the eyelids, has emerged as a potential treatment for MGD.
OBJECTIVES
To evaluate the effectiveness and safety of intense pulsed light (IPL) for the management dry eye disease resulting from meibomian gland dysfunction (MGD).
SEARCH METHODS
We searched CENTRAL, MEDLINE (Ovid), Embase Ovid and three trial registers for eligible clinical trials on 1 August 2019. There were no restrictions on publication status, date or language.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) studying the effectiveness or safety of IPL for treating MGD.
DATA COLLECTION AND ANALYSIS
Our outcomes of interest were the change from baseline in subjective dry eye symptoms, adverse events, changes to lipid layer thickness, tear break-up time (TBUT), tear osmolarity, eyelid irregularity, eyelid telangiectasia, meibomian gland orifice plugging, meibomian gland dropout, corneal sodium fluorescein staining and conjunctival lissamine green staining. Two review authors independently screened abstracts and full-text articles, extracted data from eligible RCTs and judged the risk of bias using the Cochrane tool. We reached consensus on any disagreements by discussion. We summarised the overall certainty of the evidence using the GRADE Working Group approach.
MAIN RESULTS
We included three RCTs, one from New Zealand, one from Japan and one from China, published between 2015 and 2019. Together, these trials enrolled 114 adults (228 eyes). Two studies used a paired-eye (inter-eye comparison) design to evaluate the effects of a sham (control) IPL treatment relative to an actual IPL treatment. One study randomised individuals to either an IPL intervention combined with meibomian gland expression (MGX), or MGX alone (standard therapy). The study follow-up periods ranged from 45 days to nine months. None of the trials were at low risk of bias in all seven domains. The first authors of two included studies were in receipt of funding from patents or the manufacturers of IPL devices. The funding sources and declaration of interests were not given in the report of the third included trial. All three trials evaluated the effect of IPL on dry eye symptoms, quantified using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Pooling data from two trials that used a paired-eye design, the summary estimate for these studies indicated little to no reduction in dry eye symptoms with IPL relative to a sham intervention (mean difference (MD) -0.33 units, 95% confidence interval (CI) -2.56 to 1.89; I² = 0%; 2 studies, 144 eyes). The other study was not pooled as it had a unit-of-analysis error, but reported a reduction in symptoms in favour of IPL (MD -4.60, 95% CI -6.72 to -2.48; 84 eyes). The body of evidence for this outcome was of very low certainty, so we are uncertain about the effect of IPL on dry eye symptoms. There were no relevant combinable data for any of the other secondary outcomes, thus the effect of IPL on clinical parameters relevant to dry eye disease are currently unclear. For sodium fluorescein TBUT, two studies indicated that there may be an improvement in favour of IPL (MD 2.02 seconds, 95% CI 0.87 to 3.17; MD 2.40 seconds, 95% CI 2.27 to 2.53; 172 eyes total; low-certainty evidence). We are uncertain of the effect of IPL on non-invasive tear break-up time (MD 5.51 seconds, 95% CI 0.79 to 10.23; MD 3.20, 95% CI 3.09 to 3.31 seconds; two studies; 140 eyes total; very low-certainty evidence). For tear osmolarity, one study indicated that there may be an improvement in favour of IPL (MD -7.00 mOsmol/L, 95% -12.97 to -1.03; 56 eyes; low-certainty evidence). We are uncertain of the effect of IPL on meibomian gland orifice plugging (MD -1.20 clinical units, 95% CI -1.24 to -1.16; 84 eyes; very low-certainty evidence). We are uncertain of the effect of IPL on corneal sodium fluorescein staining. One study reported no evidence of a difference between the IPL and sham intervention arms at three months of follow-up (P = 0.409), and a second study reported data favouring IPL (MD -1.00 units, 95% CI -1.07 to -0.93 units; 172 eyes in total; very low-certainty evidence). We considered the incidence of adverse events at the study endpoint, as a measure of safety. As most trials did not specifically report adverse events, the safety of IPL as a treatment for MGD could also not be determined with any certainty. Very low-certainty results from individual studies suggest some adverse effects that may be experienced by participants, include mild pain and burning, and the potential for partially losing eyelashes (due to clinician error).
AUTHORS' CONCLUSIONS
This systematic review finds a scarcity of RCT evidence relating to the effectiveness and safety of IPL as a treatment for MGD. Whether IPL is of value for modifying the symptoms or signs of evaporative dry eye disease is currently uncertain. Due to a lack of comprehensive reporting of adverse events, the safety profile of IPL in this patient population is also unclear. The current limitations in the evidence base should be considered by clinicians using this intervention to treat MGD, and outlined to individuals potentially undergoing this procedure with the intent of treating dry eye disease. The results of the 14 RCTs currently in progress will be of major importance for establishing a more definitive answer regarding the effectiveness and safety of IPL for treating MGD. We intend to update this review when results from these trials become available.
Topics: Dry Eye Syndromes; Humans; Intense Pulsed Light Therapy; Meibomian Gland Dysfunction; Randomized Controlled Trials as Topic
PubMed: 32182637
DOI: 10.1002/14651858.CD013559 -
The Cochrane Database of Systematic... Feb 2018Bronchiectasis is a long term respiratory condition with an increasing rate of diagnosis. It is associated with persistent symptoms, repeated infective exacerbations,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiectasis is a long term respiratory condition with an increasing rate of diagnosis. It is associated with persistent symptoms, repeated infective exacerbations, and reduced quality of life, imposing a burden on individuals and healthcare systems. The main aims of therapeutic management are to reduce exacerbations and improve quality of life. Self-management interventions are potentially important for empowering people with bronchiectasis to manage their condition more effectively and to seek care in a timely manner. Self-management interventions are beneficial in the management of other airways diseases such as asthma and COPD (chronic obstructive pulmonary disease) and have been identified as a research priority for bronchiectasis.
OBJECTIVES
To assess the efficacy, cost-effectiveness and adverse effects of self-management interventions for adults and children with non-cystic fibrosis bronchiectasis.
SEARCH METHODS
We searched the Cochrane Airways Specialised Register of trials, clinical trials registers, reference lists of included studies and review articles, and relevant manufacturers' websites up to 13 December 2017.
SELECTION CRITERIA
We included all randomised controlled trials of any duration that included adults or children with a diagnosis of non-cystic fibrosis bronchiectasis assessing self-management interventions delivered in any form. Self-management interventions included at least two of the following elements: patient education, airway clearance techniques, adherence to medication, exercise (including pulmonary rehabilitation) and action plans.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened searches, extracted study characteristics and outcome data and assessed risk of bias for each included study. Primary outcomes were, health-related quality of life, exacerbation frequency and serious adverse events. Secondary outcomes were the number of participants admitted to hospital on at least one occasion, lung function, symptoms, self-efficacy and economic costs. We used a random effects model for analyses and standard Cochrane methods throughout.
MAIN RESULTS
Two studies with a total of 84 participants were included: a 12-month RCT of early rehabilitation in adults of mean age 72 years conducted in two centres in England (UK) and a six-month proof-of-concept RCT of an expert patient programme (EPP) in adults of mean age 60 years in a single regional respiratory centre in Northern Ireland (UK). The EPP was delivered in group format once a week for eight weeks using standardised EPP materials plus disease-specific education including airway clearance techniques, dealing with symptoms, exacerbations, health promotion and available support. We did not find any studies that included children. Data aggregation was not possible and findings are reported narratively in the review.For the primary outcomes, both studies reported health-related quality of life, as measured by the St George's Respiratory Questionnaire (SGRQ), but there was no clear evidence of benefit. In one study, the mean SGRQ total scores were not significantly different at 6 weeks', 3 months' and 12 months' follow-up (12 months mean difference (MD) -10.27, 95% confidence interval (CI) -45.15 to 24.61). In the second study there were no significant differences in SGRQ. Total scores were not significantly different between groups (six months, MD 3.20, 95% CI -6.64 to 13.04). We judged the evidence for this outcome as low or very low. Neither of the included studies reported data on exacerbations requiring antibiotics. For serious adverse events, one study reported more deaths in the intervention group compared to the control group, (intervention: 4 of 8, control: 2 of 12), though interpretation is limited by the low event rate and the small number of participants in each group.For our secondary outcomes, there was no evidence of benefit in terms of frequency of hospital admissions or FEV1 L, based on very low-quality evidence. One study reported self-efficacy using the Chronic Disease Self-Efficacy scale, which comprises 10 components. All scales showed significant benefit from the intervention but effects were only sustained to study endpoint on the Managing Depression scale. Further details are reported in the main review. Based on overall study quality, we judged this evidence as low quality. Neither study reported data on respiratory symptoms, economic costs or adverse events.
AUTHORS' CONCLUSIONS
There is insufficient evidence to determine whether self-management interventions benefit people with bronchiectasis. In the absence of high-quality evidence it is advisable that practitioners adhere to current international guidelines that advocate self-management for people with bronchiectasis.Future studies should aim to clearly define and justify the specific nature of self-management, measure clinically important outcomes and include children as well as adults.
Topics: Aged; Bronchiectasis; Disease Progression; Forced Expiratory Volume; Hospitalization; Humans; Middle Aged; Patient Education as Topic; Quality of Life; Randomized Controlled Trials as Topic; Self Efficacy; Self-Management
PubMed: 29411860
DOI: 10.1002/14651858.CD012528.pub2 -
The Cochrane Database of Systematic... May 2017Osteoarthritis (OA) is the most common form of arthritis and is caused by degeneration of the joint cartilage and growth of new bone, cartilage and connective tissue. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoarthritis (OA) is the most common form of arthritis and is caused by degeneration of the joint cartilage and growth of new bone, cartilage and connective tissue. It is often associated with major disability and impaired quality of life. There is currently no consensus on the best treatment to improve OA symptoms. Celecoxib is a selective non-steroidal anti-inflammatory drug (NSAID).
OBJECTIVES
To assess the clinical benefits (pain, function, quality of life) and safety (withdrawals due to adverse effects, serious adverse effects, overall discontinuation rates) of celecoxib in osteoarthritis (OA).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and clinical trials registers up to April 11, 2017, as well as reference and citation lists of included studies. Pharmaceutical companies and authors of published articles were contacted.
SELECTION CRITERIA
We included published studies (full reports in a peer reviewed journal) of prospective randomized controlled trials (RCTs) that compared oral celecoxib versus no intervention, placebo or another traditional NSAID (tNSAID) in participants with clinically- or radiologically-confirmed primary OA of the knee or hip, or both knee and hip.
DATA COLLECTION AND ANALYSIS
Two authors independently performed data extraction, quality assessment, and compared results. Main analyses for patient-reported outcomes of pain and physical function were conducted on studies with low risk of bias for sequence generation, allocation concealment and blinding of participants and personnel.
MAIN RESULTS
We included 36 trials that provided data for 17,206 adults: 9402 participants received celecoxib 200 mg/day, and 7804 were assigned to receive either tNSAIDs (N = 1869) or placebo (N = 5935). Celecoxib was compared with placebo (32 trials), naproxen (6 trials) and diclofenac (3 trials). Studies were published between 1999 and 2014. Studies included participants with knee, hip or both knee and hip OA; mean OA duration was 7.9 years. Most studies included predominantly white participants whose mean age was 62 (± 10) years; most participants were women. There were no concerns about risk of bias for performance and detection bias, but selection bias was poorly reported in most trials. Most trials had high attrition bias, and there was evidence of selective reporting in a third of the studies. Celecoxib versus placeboCompared with placebo celecoxib slightly reduced pain on a 500-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale, accounting for 3% absolute improvement (95% CI 2% to 5% improvement) or 12% relative improvement (95% CI 7% to 18% improvement) (4 studies, 1622 participants). This improvement may not be clinically significant (high quality evidence).Compared with placebo celecoxib slightly improved physical function on a 1700-point WOMAC scale, accounting for 4% absolute improvement (95% CI 2% to 6% improvement), 12% relative improvement (95% CI 5% to 19% improvement) (4 studies, 1622 participants). This improvement may not be clinically significant (high quality evidence).There was no evidence of an important difference for withdrawals due to adverse events (Peto OR 0.99, 95% CI 0.85 to 1.15) (moderate quality evidence due to study limitations).Results were inconclusive for numbers of participants experiencing any serious AEs (SAEs) (Peto OR 0.95, 95% CI 0.66 to 1.36), gastro-intestinal events (Peto OR 1.91, 95% CI 0.24 to 14.90) and cardiovascular events (Peto OR 3.40, 95% CI 0.73 to 15.88) (very low quality evidence due to serious imprecision and study limitations). However, regulatory agencies have warned of increased cardiovascular events for celecoxib. Celecoxib versus tNSAIDsThere were inconclusive results regarding the effect on pain between celecoxib and tNSAIDs on a 100-point visual analogue scale (VAS), showing 5% absolute improvement (95% CI 11% improvement to 2% worse), 11% relative improvement (95% CI 26% improvement to 4% worse) (2 studies, 1180 participants, moderate quality evidence due to publication bias).Compared to a tNSAID celecoxib slightly improved physical function on a 100-point WOMAC scale, showing 6% absolute improvement (95% CI 6% to 11% improvement) and 16% relative improvement (95% CI 2% to 30% improvement). This improvement may not be clinically significant (low quality evidence due to missing data and few participants) (1 study, 264 participants).Based on low or very low quality evidence (downgraded due to missing data, high risk of bias, few events and wide confidence intervals) results were inconclusive for withdrawals due to AEs (Peto OR 0.97, 95% CI 0.74 to 1.27), number of participants experiencing SAEs (Peto OR 0.92, 95% CI 0.66 to 1.28), gastro-intestinal events (Peto OR 0.61, 0.15 to 2.43) and cardiovascular events (Peto OR 0.47, 95% CI 0.17 to 1.25).In comparisons of celecoxib and placebo there were no differences in pooled analyses between our main analysis with low risk of bias and all eligible studies. In comparisons of celecoxib and tNSAIDs, only one outcome showed a difference between studies at low risk of bias and all eligible studies: physical function (6% absolute improvement in low risk of bias, no difference in all eligible studies).No studies included in the main comparisons measured quality of life. Of 36 studies, 34 reported funding by drug manufacturers and in 34 studies one or more study authors were employees of the sponsor.
AUTHORS' CONCLUSIONS
We are highly reserved about results due to pharmaceutical industry involvement and limited data. We were unable to obtain data from three studies, which included 15,539 participants, and classified as awaiting assessment. Current evidence indicates that celecoxib is slightly better than placebo and some tNSAIDs in reducing pain and improving physical function. We are uncertain if harms differ among celecoxib and placebo or tNSAIDs due to risk of bias, low quality evidence for many outcomes, and that some study authors and Pfizer declined to provide data from completed studies with large numbers of participants. To fill the evidence gap, we need to access existing data and new, independent clinical trials to investigate benefits and harms of celecoxib versus tNSAIDs for people with osteoarthritis, with longer follow-up and more direct head-to-head comparisons with other tNSAIDs.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Diclofenac; Female; Humans; Male; Middle Aged; Naproxen; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Measurement; Placebos; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 28530031
DOI: 10.1002/14651858.CD009865.pub2 -
The Science of the Total Environment Feb 2010Most recently, renewed interest has arisen in manufactured silver nanomaterials because of their unusually enhanced physicochemical properties and biological activities... (Review)
Review
An evidence-based environmental perspective of manufactured silver nanoparticle in syntheses and applications: a systematic review and critical appraisal of peer-reviewed scientific papers.
BACKGROUND
Most recently, renewed interest has arisen in manufactured silver nanomaterials because of their unusually enhanced physicochemical properties and biological activities compared to the bulk parent materials. A wide range of applications has emerged in consumer products ranging from disinfecting medical devices and home appliances to water treatment. Because the hypothesized mechanisms that govern the fate and transport of bulk materials may not directly apply to materials at the nanoscale, there are great concerns in the regulatory and research communities about potential environmental impacts associated with the use of silver nanoparticles. In particular, the unlimited combinations of properties emerging from the syntheses and applications of silver nanoparticles are presenting an urgent need to document the predominant salt precursors, reducing agents and stabilizing agents utilized in the synthesis processes of silver nanoparticles to guide the massive efforts required for environmental risk assessment and management.
OBJECTIVES
The primary objective of this study is to present an evidence-based environmental perspective of silver nanoparticle properties in syntheses and applications. The following specific aims are designed to achieve the study objective: Aim 1--to document the salt precursors and agents utilized in synthesizing silver nanoparticles; Aim 2--to determine the characteristics of silver nanoparticles currently in use in the scientific literature when integrated in polymer matrices to form nanocomposites and combined with other metal nanoparticles to form bimetallic nanoparticles; Aim 3--to provide a summary of the morphology of silver nanoparticles; and (4) Aim 4--to provide an environmental perspective of the evidence presented in Aims 1 to 3.
METHODS
A comprehensive electronic search of scientific databases was conducted in support of the study objectives. Specific inclusion criteria were applied to gather the most pertinent research articles. Data and information extraction relied on the type of synthesis methods, that is, synthesized silver nanoparticles in general and specific applications, nanocomposites, and bimetallic techniques. The following items were gathered for: type of silver salt, solvent, reducing agent, stabilizing agent, size, and type of application/nanocomposite/bimetallic, and template (for nanocomposites). The description of evidence was presented in tabular format. The critical appraisal was analyzed in graphical format and discussed.
RESULTS
An analysis of the scientific literature suggests that most synthesis processes produce spherical silver nanoparticles with less than 20nm diameter. Silver nanoparticles are often synthesized via reduction of AgNO(3), dissolution in water, and utilization of reductants also acting as capping or stabilizing agents for the control of particle size to ensure a relatively stable suspension. Two of the most commonly used reductants and stabilizing agents are NaBH(4) and citrate which yield particles with a negative surface charge over the environmental pH range (3-10). The environmental perspectives of these parameters are discussed.
CONCLUDING REMARKS
It is expected that the antibacterial property of bulk silver is carried over and perhaps enhanced, to silver nanoparticles. Therefore, when one examines the environmental issues associated with the manufacture and use of silver nanoparticle-based products, the antibacterial effects should always be taken into account particularly at the different stages of the product lifecycle. Currently, there are two arguments in the scientific literature about the mechanisms of antimicrobial properties of silver nanoparticles as they relate to colloidal silver particles and inonic silver. Methodologies of risk assessment and control have to account for both arguments.
Topics: Environmental Pollution; Metal Nanoparticles; Nanotechnology; Particle Size; Risk Assessment; Silver
PubMed: 19945151
DOI: 10.1016/j.scitotenv.2009.11.003 -
The Cochrane Database of Systematic... Oct 2016Essential tremor is one of the most common movement disorders. Treatment primarily consists of pharmacological agents. While primidone and propranolol are... (Review)
Review
BACKGROUND
Essential tremor is one of the most common movement disorders. Treatment primarily consists of pharmacological agents. While primidone and propranolol are well-established treatments in clinical practice, they may be ineffective in 25% to 55% of patients and can produce serious adverse events in a large percentage of them. For these reasons, it is worth evaluating the treatment alternatives for essential tremor. Some specialists have suggested that pregabalin could be a potentially useful agent, but there is uncertainty about its efficacy and safety.
OBJECTIVES
To assess the effects of pregabalin versus placebo or other treatment for essential tremor in adults.
SEARCH METHODS
We performed a systematic search without language restrictions to identify all relevant trials up to December 2015. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, NICE, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (ICTRP). We handsearched grey literature and examined the reference lists of identified studies and reviews.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) of pregabalin versus placebo or any other treatments. We included studies in which the diagnosis of ET was made according to accepted and validated diagnostic criteria. We excluded studies conducted in patients presenting secondary forms of tremor or reporting only neurophysiological parameters to assess outcomes.
DATA COLLECTION AND ANALYSIS
Two reviewers independently collected and extracted data using a data collection form. We assessed the risk of bias of the body of evidence, and we used inverse variance methods to analyse continuous outcomes and measurement scales. We compared the mean difference between treatment groups, and we combined results for dichotomous outcomes using Mantel-Haenszel methods and risk differences We used Review Manager software for data management and analysis.
MAIN RESULTS
We only found one study eligible for this review (22 participants). We assessed the risk of bias for most domains as unclear. We graded the overall quality of evidence as very low. Compared to placebo, patients treated with pregabalin showed no significant improvement of motor tasks on the 36-point subscale of the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (MD -2.15 points; 95% CI -9.16 to 4.86) or on the 32-point functional abilities subscale of the TRS (MD -0.66 points; 95% CI -2.90 to 1.58).The limited evidence showed no difference in study withdrawal (Mantel-Haenszel RD -0.09; 95% CI -0.48 to 0.30) and presentation of adverse events between pregabalin and placebo (Mantel-Haenszel RD 0.18; 95% CI -0.13 to 0.50).
AUTHORS' CONCLUSIONS
The effects of pregabalin for treating essential tremor are uncertain because the quality of the evidence is very low. One small study did not highlight any effect of this treatment; however, the high risk of bias and the lack of other studies on this topic limit further conclusion.
Topics: Adult; Anticonvulsants; Essential Tremor; Humans; Middle Aged; Pregabalin; Randomized Controlled Trials as Topic; Upper Extremity
PubMed: 27763691
DOI: 10.1002/14651858.CD009682.pub2