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Associations between sleep bruxism and other sleep-related disorders in adults: a systematic review.Sleep Medicine Jan 2022Systematic reviews on sleep bruxism (SB) as a comorbid condition of other sleep-related disorders are lacking. Such reviews would contribute to the insight of sleep... (Review)
Review
OBJECTIVE
Systematic reviews on sleep bruxism (SB) as a comorbid condition of other sleep-related disorders are lacking. Such reviews would contribute to the insight of sleep clinicians into the occurrence of SB in patients with other sleep-related disorders, and into the underlying mechanisms of such comorbid associations. This systematic review aimed: 1. to determine the prevalence of SB in adults with other sleep-related disorders; and 2. to determine the associations between SB and other sleep-related disorders, and to explain the underlying mechanisms of these associations.
METHODS
A systematic search on SB and sleep-related disorders was performed in PubMed, Embase, Cochrane Library, and Web of Science to identify eligible studies published until May 15, 2020. Quality assessment was performed using the Risk of Bias Assessment tool for Non-randomized Studies.
RESULTS
Of the 1539 unique retrieved studies, 37 articles were included in this systematic review. The prevalence of SB in adult patients with obstructive sleep apnea, restless leg syndrome, periodic limb movement during sleep, sleep-related gastroesophageal reflux disease, REM behavior disorder (RBD), and sleep-related epilepsy was higher than that in the general population. The specific mechanisms behind these positive associations could not be identified.
CONCLUSIONS
SB is more prevalent in patients with the previously mentioned disorders than in the general population. Sleep arousal may be a common factor with which all the identified disorders are associated, except RBD and Parkinson's disease. The associations between SB and these identified sleep-related disorders call for more SB screening in patients with the abovementioned sleep-related disorders.
Topics: Adult; Humans; Restless Legs Syndrome; Sleep; Sleep Apnea, Obstructive; Sleep Bruxism; Sleep Wake Disorders
PubMed: 34879286
DOI: 10.1016/j.sleep.2021.11.008 -
PLoS Medicine Aug 2009Although expert opinion has asserted that there is an increased risk of violence in individuals with schizophrenia and other psychoses, there is substantial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although expert opinion has asserted that there is an increased risk of violence in individuals with schizophrenia and other psychoses, there is substantial heterogeneity between studies reporting risk of violence, and uncertainty over the causes of this heterogeneity. We undertook a systematic review of studies that report on associations between violence and schizophrenia and other psychoses. In addition, we conducted a systematic review of investigations that reported on risk of homicide in individuals with schizophrenia and other psychoses.
METHODS AND FINDINGS
Bibliographic databases and reference lists were searched from 1970 to February 2009 for studies that reported on risks of interpersonal violence and/or violent criminality in individuals with schizophrenia and other psychoses compared with general population samples. These data were meta-analysed and odds ratios (ORs) were pooled using random-effects models. Ten demographic and clinical variables were extracted from each study to test for any observed heterogeneity in the risk estimates. We identified 20 individual studies reporting data from 18,423 individuals with schizophrenia and other psychoses. In men, ORs for the comparison of violence in those with schizophrenia and other psychoses with those without mental disorders varied from 1 to 7 with substantial heterogeneity (I(2) = 86%). In women, ORs ranged from 4 to 29 with substantial heterogeneity (I(2) = 85%). The effect of comorbid substance abuse was marked with the random-effects ORs of 2.1 (95% confidence interval [CI] 1.7-2.7) without comorbidity, and an OR of 8.9 (95% CI 5.4-14.7) with comorbidity (p<0.001 on metaregression). Risk estimates of violence in individuals with substance abuse (but without psychosis) were similar to those in individuals with psychosis with substance abuse comorbidity, and higher than all studies with psychosis irrespective of comorbidity. Choice of outcome measure, whether the sample was diagnosed with schizophrenia or with nonschizophrenic psychoses, study location, or study period were not significantly associated with risk estimates on subgroup or metaregression analysis. Further research is necessary to establish whether longitudinal designs were associated with lower risk estimates. The risk for homicide was increased in individuals with psychosis (with and without comorbid substance abuse) compared with general population controls (random-effects OR = 19.5, 95% CI 14.7-25.8).
CONCLUSIONS
Schizophrenia and other psychoses are associated with violence and violent offending, particularly homicide. However, most of the excess risk appears to be mediated by substance abuse comorbidity. The risk in these patients with comorbidity is similar to that for substance abuse without psychosis. Public health strategies for violence reduction could consider focusing on the primary and secondary prevention of substance abuse. Please see later in the article for Editors' Summary.
Topics: Female; Homicide; Humans; Male; Risk Factors; Schizophrenia; Schizophrenic Psychology; Sex Factors; Substance-Related Disorders; Violence
PubMed: 19668362
DOI: 10.1371/journal.pmed.1000120 -
The Cochrane Database of Systematic... Jul 2022Schizophrenia is a disabling psychotic disorder characterised by positive symptoms of delusions, hallucinations, disorganised speech and behaviour; and negative symptoms... (Review)
Review
BACKGROUND
Schizophrenia is a disabling psychotic disorder characterised by positive symptoms of delusions, hallucinations, disorganised speech and behaviour; and negative symptoms such as affective flattening and lack of motivation. Cognitive behavioural therapy (CBT) is a psychological intervention that aims to change the way in which a person interprets and evaluates their experiences, helping them to identify and link feelings and patterns of thinking that underpin distress. CBT models targeting symptoms of psychosis (CBTp) have been developed for many mental health conditions including schizophrenia. CBTp has been suggested as a useful add-on therapy to medication for people with schizophrenia. While CBT for people with schizophrenia was mainly developed as an individual treatment, it is expensive and a group approach may be more cost-effective. Group CBTp can be defined as a group intervention targeting psychotic symptoms, based on the cognitive behavioural model. In group CBTp, people work collaboratively on coping with distressing hallucinations, analysing evidence for their delusions, and developing problem-solving and social skills. However, the evidence for effectiveness is far from conclusive.
OBJECTIVES
To investigate efficacy and acceptability of group CBT applied to psychosis compared with standard care or other psychosocial interventions, for people with schizophrenia or schizoaffective disorder.
SEARCH METHODS
On 10 February 2021, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, four other databases and two trials registries. We handsearched the reference lists of relevant papers and previous systematic reviews and contacted experts in the field for supplemental data.
SELECTION CRITERIA
We selected randomised controlled trials allocating adults with schizophrenia to receive either group CBT for schizophrenia, compared with standard care, or any other psychosocial intervention (group or individual).
DATA COLLECTION AND ANALYSIS
We complied with Cochrane recommended standard of conduct for data screening and collection. Where possible, we calculated risk ratio (RR) and 95% confidence interval (CI) for binary data and mean difference (MD) and 95% CI for continuous data. We used a random-effects model for analyses. We assessed risk of bias for included studies and created a summary of findings table using GRADE.
MAIN RESULTS
The review includes 24 studies (1900 participants). All studies compared group CBTp with treatments that a person with schizophrenia would normally receive in a standard mental health service (standard care) or any other psychosocial intervention (group or individual). None of the studies compared group CBTp with individual CBTp. Overall risk of bias within the trials was moderate to low. We found no studies reporting data for our primary outcome of clinically important change. With regard to numbers of participants leaving the study early, group CBTp has little or no effect compared to standard care or other psychosocial interventions (RR 1.22, 95% CI 0.94 to 1.59; studies = 13, participants = 1267; I = 9%; low-certainty evidence). Group CBTp may have some advantage over standard care or other psychosocial interventions for overall mental state at the end of treatment for endpoint scores on the Positive and Negative Syndrome Scale (PANSS) total (MD -3.73, 95% CI -4.63 to -2.83; studies = 12, participants = 1036; I = 5%; low-certainty evidence). Group CBTp seems to have little or no effect on PANSS positive symptoms (MD -0.45, 95% CI -1.30 to 0.40; studies =8, participants = 539; I = 0%) and on PANSS negative symptoms scores at the end of treatment (MD -0.73, 95% CI -1.68 to 0.21; studies = 9, participants = 768; I = 65%). Group CBTp seems to have an advantage over standard care or other psychosocial interventions on global functioning measured by Global Assessment of Functioning (GAF; MD -3.61, 95% CI -6.37 to -0.84; studies = 5, participants = 254; I = 0%; moderate-certainty evidence), Personal and Social Performance Scale (PSP; MD 3.30, 95% CI 2.00 to 4.60; studies = 1, participants = 100), and Social Disability Screening Schedule (SDSS; MD -1.27, 95% CI -2.46 to -0.08; studies = 1, participants = 116). Service use data were equivocal with no real differences between treatment groups for number of participants hospitalised (RR 0.78, 95% CI 0.38 to 1.60; studies = 3, participants = 235; I = 34%). There was no clear difference between group CBTp and standard care or other psychosocial interventions endpoint scores on depression and quality of life outcomes, except for quality of life measured by World Health Organization Quality of Life Assessment Instrument (WHOQOL-BREF) Psychological domain subscale (MD -4.64, 95% CI -9.04 to -0.24; studies = 2, participants = 132; I = 77%). The studies did not report relapse or adverse effects.
AUTHORS' CONCLUSIONS
Group CBTp appears to be no better or worse than standard care or other psychosocial interventions for people with schizophrenia in terms of leaving the study early, service use and general quality of life. Group CBTp seems to be more effective than standard care or other psychosocial interventions on overall mental state and global functioning scores. These results may not be widely applicable as each study had a low sample size. Therefore, no firm conclusions concerning the efficacy of group CBTp for people with schizophrenia can currently be made. More high-quality research, reporting useable and relevant data is needed.
Topics: Adult; Cognitive Behavioral Therapy; Hallucinations; Humans; Psychotic Disorders; Quality of Life; Schizophrenia
PubMed: 35866377
DOI: 10.1002/14651858.CD009608.pub2 -
The Cochrane Database of Systematic... Mar 2013This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation.
OBJECTIVES
To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies.
SEARCH METHODS
We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012.
SELECTION CRITERIA
Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology.
DATA COLLECTION AND ANALYSIS
Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables.
MAIN RESULTS
We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied.
AUTHORS' CONCLUSIONS
This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.
Topics: Acquired Immunodeficiency Syndrome; Anorexia; Appetite Stimulants; Cachexia; Humans; Megestrol Acetate; Neoplasms; Randomized Controlled Trials as Topic; Syndrome
PubMed: 23543530
DOI: 10.1002/14651858.CD004310.pub3 -
The Cochrane Database of Systematic... Apr 2010The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness.
OBJECTIVES
To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression.
SEARCH STRATEGY
MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data.
SELECTION CRITERIA
Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects).
MAIN RESULTS
A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea.
AUTHORS' CONCLUSIONS
This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.
Topics: Antidepressive Agents; Depression; Diarrhea; Humans; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome
PubMed: 20393946
DOI: 10.1002/14651858.CD006117.pub4 -
Nutrition Reviews Jul 2023Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and... (Meta-Analysis)
Meta-Analysis
The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials.
CONTEXT
Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and treat iron deficiency, despite poor bioavailability and frequently reported adverse side effects. Ferrous bisglycinate is a novel amino acid iron chelate that is thought to be more bioavailable and associated with fewer gastrointestinal (GI) adverse events as compared with iron salts.
OBJECTIVE
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of ferrous bisglycinate supplementation compared with other iron supplements on hemoglobin and ferritin concentrations and GI adverse events.
DATA SOURCES
A systematic search of electronic databases and grey literature was performed up to July 17, 2020, yielding 17 RCTs that reported hemoglobin or ferritin concentrations following at least 4 weeks' supplementation of ferrous bisglycinate compared with other iron supplements in any dose or frequency.
DATA EXTRACTION
Random-effects meta-analyses were conducted among trials of pregnant women (n = 9) and children (n = 4); pooled estimates were expressed as standardized mean differences (SMDs). Incidence rate ratios (IRRs) were estimated for GI adverse events, using Poisson generalized linear mixed-effects models. The remaining trials in other populations (n = 4; men and nonpregnant women) were qualitatively evaluated.
DATA ANALYSIS
Compared with other iron supplements, supplementation with ferrous bisglycinate for 4-20 weeks resulted in higher hemoglobin concentrations in pregnant women (SMD, 0.54 g/dL; 95% confidence interval [CI], 0.15-0.94; P < 0.01) and fewer reported GI adverse events (IRR, 0.36; 95%CI, 0.17-0.76; P < 0.01). We observed a non-significant trend for higher ferritin concentrations in pregnant women supplemented with ferrous bisglycinate. No significant differences in hemoglobin or ferritin concentrations were detected among children.
CONCLUSION
Ferrous bisglycinate shows some benefit over other iron supplements in increasing hemoglobin concentration and reducing GI adverse events among pregnant women. More trials are needed to assess the efficacy of ferrous bisglycinate against other iron supplements in other populations.
PROSPERO REGISTRATION NO
CRD42020196984.
Topics: Adult; Child; Female; Humans; Male; Pregnancy; Anemia, Iron-Deficiency; Dietary Supplements; Ferritins; Hemoglobins; Iron; Iron Deficiencies; Randomized Controlled Trials as Topic; Salts; Ferrous Compounds
PubMed: 36728680
DOI: 10.1093/nutrit/nuac106 -
Dermatology and Therapy Aug 2022Biologic treatments are increasingly being used in the management of moderate to severe plaque psoriasis (PSO). Bimekizumab is a selective inhibitor of both interleukin...
INTRODUCTION
Biologic treatments are increasingly being used in the management of moderate to severe plaque psoriasis (PSO). Bimekizumab is a selective inhibitor of both interleukin (IL)-17A and IL-17F approved for the treatment of moderate to severe PSO. Although bimekizumab trials provide comparisons to secukinumab, adalimumab and ustekinumab, there are no further head-to-head comparisons of bimekizumab to other biologics. This network meta-analysis (NMA) aimed to compare the short-term efficacy of bimekizumab versus other biologic systemic therapies for moderate to severe PSO.
METHODS
A systematic literature review was conducted to identify randomised controlled trials (RCTs) in patients with moderate to severe PSO. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Database of Systematic Reviews and PsycINFO were searched on July 1, 2020. An enhanced multinomial Bayesian NMA model was used to evaluate the comparative efficacy in 50%, 75%, 90% and 100% improvement from baseline Psoriasis Area and Severity Index (PASI 50/75/90/100) at 10-16 weeks. The model was also adjusted for baseline risk, given the variable placebo responses across the trials.
RESULTS
Eighty-six RCTs (including 34,476 patients) were included in the NMA. IL-17 and IL-23 inhibitors were the most effective treatments across all PASI levels. At 10-16 weeks, bimekizumab had the highest probability of achieving PASI 75 (92.3%), PASI 90 (84.0%) and PASI 100 (57.8%). Bimekizumab demonstrated statistical superiority over all biologics in achieving PASI 90 and PASI 100 thresholds. For PASI 75, the benefit of bimekizumab was statistically significant compared to all other treatments except risankizumab and ixekizumab.
CONCLUSION
This analysis demonstrated that IL-17 and IL-23 inhibitors were highly effective in achieving short-term improvement among patients with moderate to severe PSO. Patients receiving bimekizumab were significantly more likely to achieve PASI 90 or PASI 100 within 10-16 weeks of the first injection than all other biologics.
PubMed: 35798920
DOI: 10.1007/s13555-022-00760-8 -
European Review For Medical and... Apr 2021To evaluate the effectiveness of case-based learning (CBL) in medical students' education through meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effectiveness of case-based learning (CBL) in medical students' education through meta-analysis.
MATERIALS AND METHODS
PubMed, Cochrane Library, Elsevier and other databases were searched to find randomized controlled trials (RCTs) of CBL teaching methods and other teaching methods published from January 1, 1995, to October 1, 2020. All included studies used the Cochrane risk bias assessment tool, and Review Manager software, version 5.3 (Copenhagen, Denmark), was used for the meta-analysis and systematic review.
RESULTS
A total of 8 studies were included with a total of 939 students, including 480 in the CBL group and 459 in the control group. Compared with other teaching methods, CBL teaching can improve medical students' academic performance (p=0.03) and case analysis ability (p<0.001).
CONCLUSIONS
CBL is an active teaching method that is effective for educating medical students and helps to improve their performance and case analysis ability.
Topics: Education, Medical; Humans; Learning; Students, Medical
PubMed: 33928603
DOI: 10.26355/eurrev_202104_25726 -
Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.The Cochrane Database of Systematic... Apr 2022This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for focal onset seizures and sodium valproate for generalised onset seizures; however, a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.
OBJECTIVES
To compare the time to treatment failure, remission and first seizure of 12 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, eventrate, zonisamide, eslicarbazepine acetate, lacosamide) currently used as monotherapy in children and adults with focal onset seizures (simple focal, complex focal or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).
SEARCH METHODS
For the latest update, we searched the following databases on 12 April 2021: the Cochrane Register of Studies (CRS Web), which includes PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Epilepsy Group Specialised Register and MEDLINE (Ovid, 1946 to April 09, 2021). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators and experts in the field.
SELECTION CRITERIA
We included randomised controlled trials of a monotherapy design in adults or children with focal onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) and network meta-analysis (NMA) review. Our primary outcome was 'time to treatment failure', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', and 'time to first seizure post-randomisation'. We performed frequentist NMA to combine direct evidence with indirect evidence across the treatment network of 12 drugs. We investigated inconsistency between direct 'pairwise' estimates and NMA results via node splitting. Results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs) and we assessed the certainty of the evidence using the CiNeMA approach, based on the GRADE framework. We have also provided a narrative summary of the most commonly reported adverse events.
MAIN RESULTS
IPD were provided for at least one outcome of this review for 14,789 out of a total of 22,049 eligible participants (67% of total data) from 39 out of the 89 eligible trials (43% of total trials). We could not include IPD from the remaining 50 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions. No IPD were available from a single trial of eslicarbazepine acetate, so this AED could not be included in the NMA. Network meta-analysis showed high-certainty evidence that for our primary outcome, 'time to treatment failure', for individuals with focal seizures; lamotrigine performs better than most other treatments in terms of treatment failure for any reason and due to adverse events, including the other first-line treatment carbamazepine; HRs (95% CIs) for treatment failure for any reason for lamotrigine versus: eventrate 1.01 (0.88 to 1.20), zonisamide 1.18 (0.96 to 1.44), lacosamide 1.19 (0.90 to 1.58), carbamazepine 1.26 (1.10 to 1.44), oxcarbazepine 1.30 (1.02 to 1.66), sodium valproate 1.35 (1.09 to 1.69), phenytoin 1.44 (1.11 to 1.85), topiramate 1.50 (1.23 to 1.81), gabapentin 1.53 (1.26 to 1.85), phenobarbitone 1.97 (1.45 to 2.67). No significant difference between lamotrigine and eventrate was shown for any treatment failure outcome, and both AEDs seemed to perform better than all other AEDs. For people with generalised onset seizures, evidence was more limited and of moderate certainty; no other treatment performed better than first-line treatment sodium valproate, but there were no differences between sodium valproate, lamotrigine or eventrate in terms of treatment failure; HRs (95% CIs) for treatment failure for any reason for sodium valproate versus: lamotrigine 1.06 (0.81 to 1.37), eventrate 1.13 (0.89 to 1.42), gabapentin 1.13 (0.61 to 2.11), phenytoin 1.17 (0.80 to 1.73), oxcarbazepine 1.24 (0.72 to 2.14), topiramate 1.37 (1.06 to 1.77), carbamazepine 1.52 (1.18 to 1.96), phenobarbitone 2.13 (1.20 to 3.79), lacosamide 2.64 (1.14 to 6.09). Network meta-analysis also showed high-certainty evidence that for secondary remission outcomes, few notable differences were shown for either seizure type; for individuals with focal seizures, carbamazepine performed better than gabapentin (12-month remission) and sodium valproate (six-month remission). No differences between lamotrigine and any AED were shown for individuals with focal seizures, or between sodium valproate and other AEDs for individuals with generalised onset seizures. Network meta-analysis also showed high- to moderate-certainty evidence that, for 'time to first seizure,' in general, the earliest licensed treatments (phenytoin and phenobarbitone) performed better than the other treatments for individuals with focal seizures; phenobarbitone performed better than both first-line treatments carbamazepine and lamotrigine. There were no notable differences between the newer drugs (oxcarbazepine, topiramate, gabapentin, eventrate, zonisamide and lacosamide) for either seizure type. Generally, direct evidence (where available) and network meta-analysis estimates were numerically similar and consistent with confidence intervals of effect sizes overlapping. There was no important indication of inconsistency between direct and network meta-analysis results. The most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness and rash or skin disorders; however, reporting of adverse events was highly variable across AEDs and across studies.
AUTHORS' CONCLUSIONS
High-certainty evidence demonstrates that for people with focal onset seizures, current first-line treatment options carbamazepine and lamotrigine, as well as newer drug eventrate, show the best profile in terms of treatment failure and seizure control as first-line treatments. For people with generalised tonic-clonic seizures (with or without other seizure types), current first-line treatment sodium valproate has the best profile compared to all other treatments, but lamotrigine and eventrate would be the most suitable alternative first-line treatments, particularly for those for whom sodium valproate may not be an appropriate treatment option. Further evidence from randomised controlled trials recruiting individuals with generalised tonic-clonic seizures (with or without other seizure types) is needed.
Topics: Adult; Anticonvulsants; Child; Epilepsies, Partial; Epilepsy; Humans; Network Meta-Analysis; Phenytoin
PubMed: 35363878
DOI: 10.1002/14651858.CD011412.pub4 -
The Cochrane Database of Systematic... Mar 2020Alcohol use disorder (AUD) confers a prodigious burden of disease, disability, premature mortality, and high economic costs from lost productivity, accidents, violence,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol use disorder (AUD) confers a prodigious burden of disease, disability, premature mortality, and high economic costs from lost productivity, accidents, violence, incarceration, and increased healthcare utilization. For over 80 years, Alcoholics Anonymous (AA) has been a widespread AUD recovery organization, with millions of members and treatment free at the point of access, but it is only recently that rigorous research on its effectiveness has been conducted.
OBJECTIVES
To evaluate whether peer-led AA and professionally-delivered treatments that facilitate AA involvement (Twelve-Step Facilitation (TSF) interventions) achieve important outcomes, specifically: abstinence, reduced drinking intensity, reduced alcohol-related consequences, alcohol addiction severity, and healthcare cost offsets.
SEARCH METHODS
We searched the Cochrane Drugs and Alcohol Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, CINAHL and PsycINFO from inception to 2 August 2019. We searched for ongoing and unpublished studies via ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 15 November 2018. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and bibliographies of included studies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs), quasi-RCTs and non-randomized studies that compared AA or TSF (AA/TSF) with other interventions, such as motivational enhancement therapy (MET) or cognitive behavioral therapy (CBT), TSF treatment variants, or no treatment. We also included healthcare cost offset studies. Participants were non-coerced adults with AUD.
DATA COLLECTION AND ANALYSIS
We categorized studies by: study design (RCT/quasi-RCT; non-randomized; economic); degree of standardized manualization (all interventions manualized versus some/none); and comparison intervention type (i.e. whether AA/TSF was compared to an intervention with a different theoretical orientation or an AA/TSF intervention that varied in style or intensity). For analyses, we followed Cochrane methodology calculating the standard mean difference (SMD) for continuous variables (e.g. percent days abstinent (PDA)) or the relative risk (risk ratios (RRs)) for dichotomous variables. We conducted random-effects meta-analyses to pool effects wherever possible.
MAIN RESULTS
We included 27 studies containing 10,565 participants (21 RCTs/quasi-RCTs, 5 non-randomized, and 1 purely economic study). The average age of participants within studies ranged from 34.2 to 51.0 years. AA/TSF was compared with psychological clinical interventions, such as MET and CBT, and other 12-step program variants. We rated selection bias as being at high risk in 11 of the 27 included studies, unclear in three, and as low risk in 13. We rated risk of attrition bias as high risk in nine studies, unclear in 14, and low in four, due to moderate (> 20%) attrition rates in the study overall (8 studies), or in study treatment group (1 study). Risk of bias due to inadequate researcher blinding was high in one study, unclear in 22, and low in four. Risks of bias arising from the remaining domains were predominantly low or unclear. AA/TSF (manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) RCTs comparing manualized AA/TSF to other clinical interventions (e.g. CBT), showed AA/TSF improves rates of continuous abstinence at 12 months (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 2 studies, 1936 participants; high-certainty evidence). This effect remained consistent at both 24 and 36 months. For percentage days abstinent (PDA), AA/TSF appears to perform as well as other clinical interventions at 12 months (mean difference (MD) 3.03, 95% CI -4.36 to 10.43; 4 studies, 1999 participants; very low-certainty evidence), and better at 24 months (MD 12.91, 95% CI 7.55 to 18.29; 2 studies, 302 participants; low-certainty evidence) and 36 months (MD 6.64, 95% CI 1.54 to 11.75; 1 study, 806 participants; low-certainty evidence). For longest period of abstinence (LPA), AA/TSF may perform as well as comparison interventions at six months (MD 0.60, 95% CI -0.30 to 1.50; 2 studies, 136 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at 12 months, as measured by drinks per drinking day (DDD) (MD -0.17, 95% CI -1.11 to 0.77; 1 study, 1516 participants; moderate-certainty evidence) and percentage days heavy drinking (PDHD) (MD -5.51, 95% CI -14.15 to 3.13; 1 study, 91 participants; low-certainty evidence). For alcohol-related consequences, AA/TSF probably performs as well as other clinical interventions at 12 months (MD -2.88, 95% CI -6.81 to 1.04; 3 studies, 1762 participants; moderate-certainty evidence). For alcohol addiction severity, one study found evidence of a difference in favor of AA/TSF at 12 months (P < 0.05; low-certainty evidence). AA/TSF (non-manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) For the proportion of participants completely abstinent, non-manualized AA/TSF may perform as well as other clinical interventions at three to nine months follow-up (RR 1.71, 95% CI 0.70 to 4.18; 1 study, 93 participants; low-certainty evidence). Non-manualized AA/TSF may also perform slightly better than other clinical interventions for PDA (MD 3.00, 95% CI 0.31 to 5.69; 1 study, 93 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at nine months, as measured by DDD (MD -1.76, 95% CI -2.23 to -1.29; 1 study, 93 participants; very low-certainty evidence) and PDHD (MD 2.09, 95% CI -1.24 to 5.42; 1 study, 286 participants; low-certainty evidence). None of the RCTs comparing non-manualized AA/TSF to other clinical interventions assessed LPA, alcohol-related consequences, or alcohol addiction severity. Cost-effectiveness studies In three studies, AA/TSF had higher healthcare cost savings than outpatient treatment, CBT, and no AA/TSF treatment. The fourth study found that total medical care costs decreased for participants attending CBT, MET, and AA/TSF treatment, but that among participants with worse prognostic characteristics AA/TSF had higher potential cost savings than MET (moderate-certainty evidence).
AUTHORS' CONCLUSIONS
There is high quality evidence that manualized AA/TSF interventions are more effective than other established treatments, such as CBT, for increasing abstinence. Non-manualized AA/TSF may perform as well as these other established treatments. AA/TSF interventions, both manualized and non-manualized, may be at least as effective as other treatments for other alcohol-related outcomes. AA/TSF probably produces substantial healthcare cost savings among people with alcohol use disorder.
Topics: Adult; Alcoholics Anonymous; Alcoholism; Cognitive Behavioral Therapy; Female; Health Care Costs; Humans; Male; Middle Aged; Motivational Interviewing; Psychotherapy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32159228
DOI: 10.1002/14651858.CD012880.pub2