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The Cochrane Database of Systematic... May 2012Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS... (Review)
Review
BACKGROUND
Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients.
OBJECTIVES
To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose.
SEARCH METHODS
A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied.
SELECTION CRITERIA
Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included.
DATA COLLECTION AND ANALYSIS
Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up.
MAIN RESULTS
The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active-comparator, cross-over trial. In the completed study, adult patients with relapsing-remitting and secondary progressive MS were exposed to both acetyl L-carnitine 2 grams daily and amantadine 200 mg daily The effects of carnitine on fatigue are unclear. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55) and no patients experienced a serious adverse event in either treatment group. Mortality and quality of life were not reported.
AUTHORS' CONCLUSIONS
There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.
Topics: Acetylcarnitine; Adult; Amantadine; Fatigue; Humans; Multiple Sclerosis; Randomized Controlled Trials as Topic; Vitamin B Complex
PubMed: 22592719
DOI: 10.1002/14651858.CD007280.pub3 -
The Cochrane Database of Systematic... 2000In the years after the discovery of oral antipsychotic medications, it became clear that there was a link between stopping medication and relapse of psychotic symptoms.... (Review)
Review
BACKGROUND
In the years after the discovery of oral antipsychotic medications, it became clear that there was a link between stopping medication and relapse of psychotic symptoms. A series of long-acting preparations was developed. These depot preparations, are frequently used for those who find taking oral medication on a regular basis difficult or unacceptable. However, it has been a consistent concern that any reduction in relapse rate afforded by the depot preparations may be offset by an increase in undesirable side effects. There is one oral preparation and two depot forms (enanthate (Moditen) and decanoate (Modecate)). The decanoate form is more frequently used but both versions were reviewed in this work.
OBJECTIVES
To compare depot fluphenazine medication to oral fluphenazine for treatment of schizophrenia.
SEARCH STRATEGY
Electronic searches of Biological Abstracts, CSG's Register, EMBASE, LILACS, MEDLINE, PsycLIT, SCISEARCH, hand searching the references of all identified studies and contacting the manufacturers of the compounds.
SELECTION CRITERIA
All randomised clinical trials that compared fluphenazine enanthate or fluphenazine decanoate to oral fluphenazine for people with schizophrenia or other psychoses were included.
DATA COLLECTION AND ANALYSIS
One reviewer (CEA) inspected study citations and then the second reviewer (ME) independently inspected 20% of citations to ensure reliability. Full reports of the studies of agreed relevance were obtained and data extracted in the same manner by the authors. Trials were allocated to three quality categories, as described in the Cochrane Collaboration Handbook. Data were analysed on an intention-to-treat basis, and, where possible, parametric continuous data were presented. Tests for heterogeneity were undertaken.
MAIN RESULTS
Data were very limited. There was no difference between fluphenazine hydrochloride and its depot form for outcomes such as global impression of functioning, relapse/re-hospitalisation, poor initial response to treatment, leaving the study early, depressed mood / suicide and side effects such as movement disorders, uncomfortable dry mouth, sleep problems and weight gain were equally common in both groups. Direct measures of mental state, social functioning and satisfaction with care were either not measured or presented in such as way as to make any analysis impossible.
REVIEWER'S CONCLUSIONS
All six included studies relate to people with schizophrenia who are already stable on oral fluphenazine or seem contented to stay in the studies. How the data from this review relate to everyday psychiatric practices, where compliance with medication is more problematic, is debatable. The use of depot fluphenazine continues to be based on clinical judgement rather than evidence from methodical evaluation within trials. A large pragmatic randomized controlled trial is long overdue.
Topics: Antipsychotic Agents; Delayed-Action Preparations; Fluphenazine; Humans; Schizophrenia
PubMed: 10796340
DOI: 10.1002/14651858.CD000307 -
The Lancet. Respiratory Medicine Jan 2023Influenza vaccines require annual readministration; however, several reports have suggested that repeated vaccination might attenuate the vaccine's effectiveness. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Influenza vaccines require annual readministration; however, several reports have suggested that repeated vaccination might attenuate the vaccine's effectiveness. We aimed to estimate the reduction in vaccine effectiveness associated with repeated influenza vaccination.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and CINAHL Complete databases for articles published from Jan 1, 2016, to June 13, 2022, and Web of Science for studies published from database inception to June 13, 2022. For studies published before Jan 1, 2016, we consulted published systematic reviews. Two reviewers (EJ-G and EJR) independently screened, extracted data using a data collection form, assessed studies' risk of bias using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) and evaluated the weight of evidence by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included observational studies and randomised controlled trials that reported vaccine effectiveness against influenza A(H1N1)pdm09, influenza A(H3N2), or influenza B using four vaccination groups: current season; previous season; current and previous seasons; and neither season (reference). For each study, we calculated the absolute difference in vaccine effectiveness (ΔVE) for current season only and previous season only versus current and previous season vaccination to estimate attenuation associated with repeated vaccination. Pooled vaccine effectiveness and ∆VE were calculated by season, age group, and overall. This study is registered with PROSPERO, CRD42021260242.
FINDINGS
We identified 4979 publications, selected 681 for full review, and included 83 in the systematic review and 41 in meta-analyses. ΔVE for vaccination in both seasons compared with the current season was -9% (95% CI -16 to -1, I=0%; low certainty) for influenza A(H1N1)pdm09, -18% (-26 to -11, I=7%; low certainty) for influenza A(H3N2), and -7% (-14 to 0, I=0%; low certainty) for influenza B, indicating lower protection with consecutive vaccination. However, for all types, A subtypes and B lineages, vaccination in both seasons afforded better protection than not being vaccinated.
INTERPRETATION
Our estimates suggest that, although vaccination in the previous year attenuates vaccine effectiveness, vaccination in two consecutive years provides better protection than does no vaccination. The estimated effects of vaccination in the previous year are concerning and warrant additional investigation, but are not consistent or severe enough to support an alternative vaccination regimen at this time.
FUNDING
WHO and the US National Institutes of Health.
Topics: Humans; Influenza, Human; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza Vaccines; Vaccination; Seasons
PubMed: 36152673
DOI: 10.1016/S2213-2600(22)00266-1 -
The Cochrane Database of Systematic... Apr 2008Lifestyle changes and cardiovascular prevention measures are a primary treatment for intermittent claudication (IC). Symptomatic treatment with vasoactive agents... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lifestyle changes and cardiovascular prevention measures are a primary treatment for intermittent claudication (IC). Symptomatic treatment with vasoactive agents (Anatomic Therapeutic Chemical Classification (ATC) for medicines from the World Health Organisation class CO4A) is controversial.
OBJECTIVES
To evaluate evidence on the efficacy and safety of oral naftidrofuryl (ATC CO4 21) versus placebo on the pain-free walking distance (PFWD) of people with IC by using a meta-analysis based on individual patient data (IPD).
SEARCH STRATEGY
The Cochrane Peripheral Vascular Diseases Group searched their Trials Register (last searched December 2007) and CENTRAL (last searched 2007, Issue 4). We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts, the Science Citation Index and contacted the authors and checked the reference lists of retrieved articles. We asked the manufacturing company for IPD.
SELECTION CRITERIA
We included only randomized controlled trials (RCTs) with low or moderate risk of bias for which the IPD were available.
DATA COLLECTION AND ANALYSIS
We collected data from the electronic data file or from the case report form and checked the data by a statistical quality control procedure. All randomized patients were analyzed following the intention-to-treat (ITT) principle. The geometric mean of the relative improvement in PFWD was calculated for both treatment groups in all identified studies. The effect of the drug was assessed compared with placebo on final walking distance (WDf) using multilevel and random-effect models and adjusting for baseline walking distance (WD0). For the responder analysis, therapeutic success was defined as an improvement of walking distance of at least 50%.
MAIN RESULTS
We included seven studies in the IPD (n = 1266 patients). One of these studies (n = 183) was only used in the sensitivity analysis so that the main analysis included 1083 patients. The ratio of the relative improvement in PFWD (naftidrofuryl compared with placebo) was 1.37 (95% confidence interval (CI) 1.32 to 1.51, P < 0.001). The absolute difference in responder rate, or proportion successfully treated, was 22.3% (95% CI 17.1% to 27.6%). The calculated number needed to treat was 4.5 (95% CI 3.6 to 5.8).
AUTHORS' CONCLUSIONS
Naftidrofuryl has a statistically significant and clinically meaningful effect of improving walking distance in the six months after initiation of therapy for people with intermittent claudication. Access by researchers to data from RCTs that is suitable for IPD analysis should be possible through repositories of data from pharmacological trials. Regular formal appraisal of the balance of risk and benefit is needed for older pharmaceutical products.
Topics: Administration, Oral; Humans; Intermittent Claudication; Nafronyl; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 18425872
DOI: 10.1002/14651858.CD001368.pub3 -
Health Technology Assessment... 2012Chronic myeloid leukaemia (CML) is a form of cancer affecting the blood, characterised by excessive proliferation of white blood cells in the bone marrow and circulating... (Review)
Review
BACKGROUND
Chronic myeloid leukaemia (CML) is a form of cancer affecting the blood, characterised by excessive proliferation of white blood cells in the bone marrow and circulating blood. In the UK, an estimated 560 new cases of CML are diagnosed each year.
OBJECTIVES
The purpose of this study was to assess the clinical effectiveness and cost-effectiveness of dasatinib and nilotinib in the treatment of people with imatinib-resistant (ImR) and imatinib-intolerant (ImI) CML. A systematic review of the clinical effectiveness literature, a review of manufacturer submissions and a critique and exploration of manufacturer submissions for accelerated phase and blast crisis CML were carried out and a decision-analytic model was developed to estimate the cost-effectiveness of dasatinib and nilotinib in chronic phase CML. SYSTEMATIC REVIEW METHODS: Key databases were searched for relevant studies from their inception to June 2009 [MEDLINE (including MEDLINE In-Process & Other Non-Indexed Citations), EMBASE, (ISI Web of Science) Conference Proceedings Citation Index and four others]. One reviewer assessed titles and abstracts of studies identified by the search strategy, with a sample checked by a second reviewer. The full text of relevant papers was obtained and screened against the full inclusion criteria independently by two reviewers. Data from included studies were extracted by one reviewer and checked by a second. Clinical effectiveness studies were synthesised through narrative review. ECONOMIC EVALUATION METHODS: Cost-effectiveness analyses reported in manufacturer submissions to the National Institute of Health and Clinical Excellence were critically appraised and summarised narratively. In addition, the models for accelerated phase and blast crisis underwent a more detailed critique and exploration. Two separate decision-analytic models were developed for chronic phase CML, one simulating a cohort of individuals who have shown or developed resistance to normal dose imatinib and one representing individuals who have been unable to continue imatinib treatment owing to adverse events. One-way, multiway and probabilistic sensitivity analyses were performed to explore structural and parameter uncertainty.
RESULTS
Fifteen studies were included in the systematic review. Chronic phase: effectiveness data were limited but dasatinib and nilotinib appeared efficacious in terms of obtaining cytogenetic response and haematological response in both ImR and ImI populations. In terms of cost-effectiveness, it was extremely difficult to reach any conclusions regarding either agent in the ImR population. All three models (Novartis, PenTAG and Bristol-Myers Squibb) were seriously flawed in one way or another, as a consequence of the paucity of data appropriate to construct robust decision-analytic models. Accelerated and blast crisis: all available data originated from observational single-arm studies and there were considerable and potentially important differences in baseline characteristics which seriously undermined any process for making meaningful comparisons between treatments. Owing to a lack of available clinical data, de novo models of accelerated phase and blast crisis have not been developed. The economic evaluations carried out by the manufacturers of nilotinib and dasatinib were seriously undermined by the absence of evidence on high-dose imatinib in these populations.
LIMITATIONS
The study has been necessarily constrained by the paucity of available clinical data, the differences in definitions used in the studies and the subsequent impossibility of undertaking a meaningful cost-effectiveness analyses to inform all policy questions.
CONCLUSIONS
Dasatinib and nilotinib appeared efficacious in terms of obtaining cytogenetic and haematological responses in both ImR and ImI populations. It was difficult to reach any cost-effectiveness conclusions as a consequence of the paucity of the data. Future research should include a three-way, double-blind, randomised clinical trial of dasatinib, nilotinib and high-dose imatinib.
Topics: Benzamides; Blast Crisis; Clinical Trials as Topic; Cost-Benefit Analysis; Dasatinib; Decision Support Techniques; Disease Progression; Drug Resistance, Neoplasm; Health Care Costs; Humans; Imatinib Mesylate; Incidence; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic-Phase; Models, Economic; Piperazines; Prognosis; Protein Kinase Inhibitors; Pyrimidines; Quality of Life; Thiazoles
PubMed: 22551803
DOI: 10.3310/hta16220 -
The Journal of Pharmacy Technology :... Oct 2021Inhalation is the preferred method of delivering medication for respiratory conditions such as asthma, chronic obstructive pulmonary disease, and other respiratory... (Review)
Review
Inhalation is the preferred method of delivering medication for respiratory conditions such as asthma, chronic obstructive pulmonary disease, and other respiratory disease. A nebulizer converts a medication in liquid form to mist, so that the medication can be inhaled into the lungs. The aim of the study is to systematically review the knowledge, attitude, and practice of patients using nebulization therapy at home. The objective of the study is to review the procedure of nebulizer technique and to interpret the outcome of the studies. Scopus, PubMed, , and other database from 2000 to 2020 were searched using Boolean operators. Title and abstract were screened for nebulizer technology and for inclusion and exclusion criteria. After full text screening 16 articles were included in the study. Use of nebulizer at home was a challenge at all stages including setting up and operating nebulizer, filling up of medication, inhalation technique, end point dismantling, and maintenance. The main challenge experienced by the participants was with cleaning and disinfecting of nebulizer. There were studies that reported with 71.6% pathogen contamination due to inappropriate cleaning and disinfecting. Patients with respiratory disease using nebulizers at home find difficulty in appropriate and rational use of the device. Apart from the nebulizer user guidelines from the manufactures, it is suggested that a short audio visual demonstrating the appropriate and effective use of nebulizers and also its maintenance in their colloquial language with handout infographics would highly facilitate the effective use of nebulizers.
PubMed: 34752576
DOI: 10.1177/87551225211031331 -
Health Technology Assessment... Aug 2016End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival.
OBJECTIVES
To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation.
DATA SOURCES
Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and EconLit (via EBSCOhost).
REVIEW METHODS
Titles and abstracts were screened according to predefined inclusion criteria, as were full texts of identified studies. Included studies were extracted and quality appraised. Data were meta-analysed when appropriate. A new discrete time state transition economic model (semi-Markov) was developed; graft function, and incidences of acute rejection and new-onset diabetes mellitus were used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death.
RESULTS
Three randomised controlled trials (RCTs) and four non-RCTs were included. The RCTs only evaluated BAS and tacrolimus (TAC). No statistically significant differences in key outcomes were found between BAS and placebo/no induction. Statistically significantly higher graft function (p < 0.01) and less biopsy-proven acute rejection (odds ratio 0.29, 95% confidence interval 0.15 to 0.57) was found between TAC and ciclosporin (CSA). Only one cost-effectiveness study was identified, which informed NICE guidance TA99. BAS [with TAC and azathioprine (AZA)] was predicted to be cost-effective at £20,000-30,000 per quality-adjusted life year (QALY) versus no induction (BAS was dominant). BAS (with CSA and MMF) was not predicted to be cost-effective at £20,000-30,000 per QALY versus no induction (BAS was dominated). TAC (with AZA) was predicted to be cost-effective at £20,000-30,000 per QALY versus CSA (TAC was dominant). A model based on adult evidence suggests that at a cost-effectiveness threshold of £20,000-30,000 per QALY, BAS and TAC are cost-effective in all considered combinations; MMF was also cost-effective with CSA but not TAC.
LIMITATIONS
The RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence.
CONCLUSIONS
TAC is likely to be cost-effective (vs. CSA, in combination with AZA) at £20,000-30,000 per QALY. Analysis based on one RCT found BAS to be dominant, but analysis based on another RCT found BAS to be dominated. BAS plus TAC and AZA was predicted to be cost-effective at £20,000-30,000 per QALY when all regimens were compared using extrapolated adult evidence. High-quality primary effectiveness research is needed. The UK Renal Registry could form the basis for a prospective primary study.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42014013544.
FUNDING
The National Institute for Health Research HTA programme.
Topics: Abatacept; Antibodies, Monoclonal; Antilymphocyte Serum; Azathioprine; Basiliximab; Child; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Therapy, Combination; Everolimus; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Models, Economic; Mycophenolic Acid; Recombinant Fusion Proteins; Sirolimus; Tacrolimus; Technology Assessment, Biomedical
PubMed: 27557331
DOI: 10.3310/hta20610 -
International Archives of Occupational... Jan 2017To conduct a systematic review of epidemiologic studies on risk of cancer from exposure to silicon carbide (SiC). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To conduct a systematic review of epidemiologic studies on risk of cancer from exposure to silicon carbide (SiC).
METHODS
We followed established guidelines to search electronic databases for studies on populations exposed to SiC. We conducted meta-analyses when the data justified it.
RESULTS
We identified two studies of SiC production workers and several studies of users. The studies of production workers indicated an increased risk of lung cancer. The increased risk was restricted to workers with elevated dust exposure and, in the most informative study from Norway, was linked to estimated cristobalite exposure, a form of crystalline silica. Increased risk was not linked to SiC particles, once cristobalite exposure was controlled for. Studies of SiC users in various industries did not reveal an increased risk of lung cancer.
CONCLUSIONS
The increased risk of lung cancer detected in the SiC production industry appears to be associated with high exposure levels to total dust, including crystalline silica and cristobalite which occurred in this industry in the past decades. It may not persist under current exposure circumstances, characterized by lower levels and use of personal protection equipment. Commercial users of SiC-based products were not affected.
Topics: Carbon Compounds, Inorganic; Dust; Humans; Lung Neoplasms; Manufacturing Industry; Occupational Diseases; Occupational Exposure; Risk Factors; Silicon Compounds; Silicon Dioxide
PubMed: 27628329
DOI: 10.1007/s00420-016-1169-8 -
Neurosurgical Focus Feb 2017OBJECTIVE Cervical disc arthroplasty (CDA) has been demonstrated to be an effective treatment modality for single-level cervical radiculopathy or myelopathy. Its... (Review)
Review
OBJECTIVE Cervical disc arthroplasty (CDA) has been demonstrated to be an effective treatment modality for single-level cervical radiculopathy or myelopathy. Its advantages over an anterior cervical discectomy and fusion (ACDF) include motion preservation and decreased reoperations at the index and adjacent segments up to 7 years postoperatively. Considering the fact that many patients have multilevel cervical disc degeneration (CDD), the authors performed a systematic review of the clinical studies evaluating patients who underwent multilevel CDA (2 or more levels). METHODS A systematic review in the MEDLINE database was performed. Clinical studies including patients who had multilevel CDA were selected and included. Case reports and literature reviews were excluded. Articles were then grouped according to their main study objective: 1) studies comparing multilevel CDA versus ACDF; 2) studies comparing single-level CDA versus multilevel CDA; and 3) multilevel CDA after a previous cervical spine surgery. RESULTS Fourteen articles met all inclusion criteria. The general conclusions were that multilevel CDA was at least as safe and effective as ACDF, with preservation of cervical motion when compared with ACDF and potentially with fewer reoperations expected in most of the studies. Multilevel CDAs are clinically effective as single-level surgeries, with good clinical and radiological outcomes. Some studies reported a higher incidence of heterotopic ossification in multilevel CDA when compared with single-level procedures, but without clinical relevance during the follow-up period. A CDA may be indicated even after a previous cervical surgery in selected cases. CONCLUSIONS The current literature supports the use of multilevel CDA. Caution is necessary regarding the more restrictive indications for CDA when compared with ACDF. Further prospective, controlled, multicenter, and randomized studies not sponsored by the device manufactures are desirable to prove the superiority of CDA surgery over ACDF as the treatment of choice for CDD in selected cases.
Topics: Humans; Intervertebral Disc; MEDLINE; Range of Motion, Articular; Spinal Diseases; Spinal Fusion; Total Disc Replacement
PubMed: 28142256
DOI: 10.3171/2016.10.FOCUS16354 -
BMJ (Clinical Research Ed.) Apr 2014To describe the potential benefits and harms of oseltamivir by reviewing all clinical study reports (or similar document when no clinical study report exists) of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To describe the potential benefits and harms of oseltamivir by reviewing all clinical study reports (or similar document when no clinical study report exists) of randomised placebo controlled trials and regulatory comments ("regulatory information").
DESIGN
Systematic review of regulatory information.
DATA SOURCES
Clinical study reports, trial registries, electronic databases, regulatory archives, and correspondence with manufacturers.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised placebo controlled trials on adults and children who had confirmed or suspected exposure to natural influenza.
MAIN OUTCOME MEASURES
Time to first alleviation of symptoms, influenza outcomes, complications, admissions to hospital, and adverse events in the intention to treat population.
RESULTS
From the European Medicines Agency and Roche, we obtained clinical study reports for 83 trials. We included 23 trials in stage 1 (reliability and completeness screen) and 20 in stage 2 (formal analysis). In treatment trials on adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval 8.4 to 25.1 hours, P<0.001). There was no effect in children with asthma, but there was an effect in otherwise healthy children (mean difference 29 hours, 95% confidence interval 12 to 47 hours, P=0.001). In treatment trials there was no difference in admissions to hospital in adults (risk difference 0.15%, 95% confidence interval -0.91% to 0.78%, P=0.84) and sparse data in children and for prophylaxis. In adult treatment trials, oseltamivir reduced investigator mediated unverified pneumonia (risk difference 1.00%, 0.22% to 1.49%; number needed to treat to benefit (NNTB) 100, 95% confidence interval 67 to 451). The effect was not statistically significant in the five trials that used a more detailed diagnostic form for "pneumonia," and no clinical study reports reported laboratory or diagnostic confirmation of "pneumonia." The effect on unverified pneumonia in children and for prophylaxis was not significant. There was no significant reduction in risk of unverified bronchitis, otitis media, sinusitis, or any complication classified as serious or that led to study withdrawal. 14 of 20 trials prompted participants to self report all secondary illnesses to an investigator. Oseltamivir in the treatment of adults increased the risk of nausea (risk difference 3.66%, 0.90% to 7.39%; number needed to treat to harm (NNTH) 28, 95% confidence interval 14 to 112) and vomiting (4.56%, 2.39% to 7.58%; 22, 14 to 42). In treatment of children, oseltamivir induced vomiting (5.34%, 1.75% to 10.29%; 19, 10 to 57). In prophylaxis trials, oseltamivir reduced symptomatic influenza in participants by 55% (3.05%, 1.83% to 3.88%; NNTB 33, 26 to 55) and households (13.6%, 9.52% to 15.47%; NNTB 7, 6 to 11) based on one study, but there was no significant effect on asymptomatic influenza and no evidence of a reduction in transmission. In prophylaxis studies, oseltamivir increased the risk of psychiatric adverse events during the combined "on-treatment" and "off-treatment" periods (risk difference 1.06%, 0.07% to 2.76%; NNTH 94, 36 to 1538) and there was a dose-response effect on psychiatric events in two "pivotal" treatment trials of oseltamivir, at 75 mg (standard dose) and 150 mg (high dose) twice daily (P=0.038). In prophylaxis studies, oseltamivir increased the risk of headaches on-treatment (risk difference 3.15%, 0.88% to 5.78%; NNTH 32, 18 to 115), renal events with treatment (0.67%, -0.01% to 2.93%), and nausea while receiving treatment (4.15%, 0.86% to 9.51%; NNTH 25, 11 to 116).
CONCLUSIONS
In prophylactic studies oseltamivir reduces the proportion of symptomatic influenza. In treatment studies it also modestly reduces the time to first alleviation of symptoms, but it causes nausea and vomiting and increases the risk of headaches and renal and psychiatric syndromes. The evidence of clinically significant effects on complications and viral transmission is limited because of rarity of such events and problems with study design. The trade-off between benefits and harms should be borne in mind when making decisions to use oseltamivir for treatment, prophylaxis, or stockpiling.
Topics: Adult; Age Factors; Antiviral Agents; Child; Headache; Humans; Influenza, Human; Kidney Diseases; Nausea; Oseltamivir; Randomized Controlled Trials as Topic; Treatment Outcome; Vomiting
PubMed: 24811411
DOI: 10.1136/bmj.g2545