Summary
The inverse of the difference between rates, called the ‘number needed to treat’ (NNT), was suggested 20 years ago as a good way to present the results of comparisons of success or failure ...under different therapies. Such comparisons usually arise in randomised controlled trials and meta‐analysis. This article reviews the claims made about this statistic, and the problems associated with it. Methods that have been proposed for confidence intervals are evaluated, and shown to be erroneous. We suggest that giving the baseline risk, and the difference in success or event rates, the ‘absolute risk reduction’, is preferable to the number needed to treat, for both theoretical and practical reasons.
Background
The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 20% of patients from population‐based studies, ...and up to 30% from clinical series (not population‐based), develop drug‐resistant epilepsy, especially those with focal‐onset seizures. In this review, we summarise the current evidence regarding topiramate, an antiepileptic drug first marketed in 1996, when used as an add‐on treatment for drug‐resistant focal epilepsy.
This is an update of a Cochrane Review first published in 1999, and last updated in 2014.
Objectives
To evaluate the efficacy and tolerability of topiramate when used as an add‐on treatment for people with drug‐resistant focal epilepsy.
Search methods
For the latest update of this review we searched the following databases on 2 July 2018: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (Ovid, 1946‐ ); ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We also contacted the manufacturers of topiramate and researchers in the field to identify any ongoing or unpublished studies.
Selection criteria
Randomised, placebo‐controlled add‐on trials of topiramate, recruiting people with drug‐resistant focal epilepsy.
Data collection and analysis
Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: (1) 50% or greater reduction in seizure frequency; (2) seizure freedom; (3) treatment withdrawal (any reason); (4) adverse effects. Primary analyses were intention‐to‐treat (ITT), and summary risk ratios (RRs) with 95% confidence intervals (95% CIs) are presented. We evaluated dose‐response in regression models. We carried out a 'Risk of bias' assessment for each included study using the Cochrane 'Risk of bias' tool and assessed the overall certainty of evidence using the GRADE approach.
Main results
We included 12 trials, representing 1650 participants. Baseline phases ranged from four to 12 weeks and double‐blind phases ranged from 11 to 19 weeks. The RR for a 50% or greater reduction in seizure frequency with add‐on topiramate compared to placebo was 2.71 (95% CI 2.05 to 3.59; 12 studies; high‐certainty evidence). Dose regression analysis showed increasing effect with increasing topiramate dose demonstrated by an odds ratio (OR) of 1.45 (95% CI 1.28 to 1.64; P < 0.001) per 200 mg/d increase in topiramate dosage. The proportion of participants achieving seizure freedom was also significantly increased with add‐on topiramate compared to placebo (RR 3.67, 95% CI 1.79 to 7.54; 8 studies; moderate‐certainty evidence). Treatment withdrawal was significantly higher for add‐on topiramate compared to placebo (RR 2.37, 95% CI 1.66 to 3.37; 12 studies; high‐certainty evidence). The RRs for the following adverse effects indicate that they are significantly more prevalent with topiramate, compared to placebo: ataxia 2.29 (99% CI 1.10 to 4.77; 4 studies); concentration difficulties 7.81 (99% CI 2.08 to 29.29; 6 studies; moderate‐certainty evidence); dizziness 1.52 (99% CI 1.07 to 2.16; 8 studies); fatigue 2.08 (99% CI 1.37 to 3.15; 10 studies); paraesthesia 3.65 (99% CI 1.58 to 8.39; 7 studies; moderate‐certainty evidence); somnolence 2.44 (99% CI 1.61 to 3.68; 9 studies); 'thinking abnormally' 5.70 (99% CI 2.26 to 14.38; 4 studies; high‐certainty evidence); and weight loss 3.99 (99% CI 1.82 to 8.72; 9 studies; low‐certainty evidence). Evidence of publication bias for the primary outcome was found (Egger test, P = 0.001). We rated all studies included in the review as having either low or unclear risk of bias. Overall, we assessed the evidence as moderate to high certainty due to the evidence of publication bias, statistical heterogeneity and imprecision, which was partially compensated for by large effect sizes.
Authors' conclusions
Topiramate has efficacy as an add‐on treatment for drug‐resistant focal epilepsy as it is almost three times more effective compared to a placebo in reducing seizures. The trials reviewed were of relatively short duration and provided no evidence for the long‐term efficacy of topiramate. Short‐term use of add‐on topiramate was shown to be associated with several adverse events. The results of this review should only be applied to adult populations as only one study included children. Future research should consider further examining the effect of dose.
Background
Drug resistance is common in focal epilepsy. In this update, we summarised the current evidence regarding add‐on levetiracetam in treating drug‐resistant focal epilepsy. The original ...review was published in 2001 and last updated in 2012.
Objectives
To evaluate the effectiveness of levetiracetam when used as an add‐on treatment for people with drug‐resistant focal epilepsy.
Search methods
We searched the Cochrane Register of Studies (CRS Web, which includes the Cochrane Epilepsy Group Specialized Register and CENTRAL), MEDLINE Ovid, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) to November 2018. We contacted the manufacturers of levetiracetam and researchers in the field to seek any ongoing or unpublished trials.
Selection criteria
Randomised, placebo‐controlled trials of add‐on levetiracetam treatment in people with drug‐resistant focal epilepsy.
Data collection and analysis
Two review authors independently selected trials for inclusion, assessed trials for bias, extracted data, and evaluated the overall certainty of the evidence. Outcomes investigated included 50% or greater reduction in focal seizure frequency (response), treatment withdrawal, adverse effects (including a specific analysis of changes in behaviour), cognitive effects, and quality of life (QoL). Primary analysis was intention‐to‐treat. We performed meta‐analysis for all outcomes using a Mantel‐Haenszel approach and calculated risk ratios (RR), with 95% confidence intervals (CI) for all estimates apart from adverse effects (99% CIs). We assessed heterogeneity using a Chi² test and the I² statistic.
Main results
This update included 14 trials (2455 participants), predominantly possessing low risks of bias. Participants were adults in 12 trials (2159 participants) and children in the remaining two (296 participants). The doses of levetiracetam tested were 500 mg/day to 4000 mg/day in adults, and 60 mg/kg/day in children. Treatment ranged from 12 to 24 weeks. When individual doses were examined, levetiracetam at either 500 mg/day or 4000 mg/day did not perform better than placebo for the 50% or greater reduction in seizure frequency outcome (500 mg: RR 1.60, 95% CI 0.71 to 3.62; P = 0.26; 4000 mg: RR 1.64, 95% CI 0.59 to 4.57; P = 0.34). Levetiracetam was significantly better than placebo at all other individual doses (1000 mg to 3000 mg). RR was significantly in favour of levetiracetam compared to placebo when results were pooled across all doses (RR 2.37, 95% CI 2.02 to 2.78; 14 studies, 2455 participants; moderate‐certainty evidence). Dose–response analysis demonstrated that the odds of achieving response (50% or greater reduction in seizure frequency) were increased by nearly 40% (odds ratio (OR) 1.39, 95% CI 1.23 to 1.58) for each 1000 mg increase in dose of levetiracetam. There were important levels of heterogeneity across multiple comparisons.
Participants were not significantly more likely to experience treatment withdrawal with levetiracetam than with placebo (pooled RR 1.11, 95% CI 0.89 to 1.40; 13 studies, 2428 participants; high‐certainty evidence).
Somnolence was the most common adverse effect, affecting 13% of participants, and it was significantly associated with levetiracetam compared to placebo (pooled RR 1.62, 99% CI 1.19 to 2.20; 13 studies, 2423 participants; moderate‐certainty evidence). Changes in behaviour were negligible in adults (1% affected; RR 1.79, 99% CI 0.59 to 5.41), but significant in children (23% affected; RR 1.90, 99% CI 1.16 to 3.11). Levetiracetam had a positive effect on some aspects of cognition and QoL in adults and worsened certain aspects of child behaviour.
Authors' conclusions
Overall, this review update finds that in both adults and children with drug‐resistant focal epilepsy, levetiracetam added on to usual care is more effective than placebo at reducing seizure frequency, it is unlikely to be stopped by patients, and it has minimal adverse effects outside of potential worsening behaviour in children. These findings are unchanged from the previous review update in 2012. This review update contributes two key additional findings: 1. a 500 mg daily dose of levetiracetam is no more effective than placebo at reducing seizures; and 2. the odds of response (50% reduction in seizure frequency) are increased by nearly 40% for each 1000 mg increase in dose of levetiracetam.
It seems reasonable to continue the use of levetiracetam in both adults and children with drug‐resistant focal epilepsy.
Therapists and other health professionals might benefit from interventions that increase their self-compassion and other-focused concern since these may strengthen their relationships with clients, ...reduce the chances of empathetic distress fatigue and burnout and increase their well-being. This article aimed to review the effectiveness of mindfulness-based interventions (MBIs) and loving-kindness mediation (LKM) in cultivating clinicians’ self-compassion and other-focused concern. Despite methodological limitations, the studies reviewed offer some support to the hypothesis that MBIs can increase self-compassion in health professionals, but provide a more mixed picture with regard to MBIs’ affect on other-focused concern. The latter finding may in part be due to ceiling effects; therefore future research, employing more sensitive measures, would be beneficial. Turning to LKM, there is encouraging preliminary evidence from non-clinician samples that LKM, or courses including LKM and related practices, can increase self-compassion and other-focused concern. As well as extending the LKM evidence base to health professionals and using more robust, large-scale designs, future research could usefully seek to identify the characteristics of people who find LKM challenging and the supports necessary to teach them LKM safely.
Nausea and vomiting in pregnancy is usually called 'morning sickness'. This is felt by sufferers to trivialise the condition. Symptoms have been described as occurring both before and after noon, but ...daily symptom patterns have not been clearly described and statistically modelled to enable the term 'morning sickness' to be accurately analysed.
To describe the daily variation in nausea and vomiting symptoms during early pregnancy in a group of sufferers.
A prospective cohort study of females recruited from 15 May 2014 to 17 February 2017 by Swiss Precision Diagnostics (SPD) Development Company Limited, which was researching hormone levels in early pregnancy and extended its study to include the description of pregnancy symptoms.
Daily symptom diaries of nausea and vomiting were kept by females who were trying to conceive. They also provided daily urine samples, which when analysed enabled the date of ovulation to be determined. Data from 256 females who conceived during the first month of the study are included in this article. Daily symptom patterns and changes in daily patterns by week of pregnancy were modelled. Functional data analysis was used to produce estimated symptom probability functions.
There was a peak probability of nausea in the morning, a lower but sustained probability of nausea throughout the day, and a slight peak in the evening. Vomiting had a defined peak incidence in the morning.
Referring to nausea and vomiting in pregnancy as simply 'morning sickness' is inaccurate, simplistic, and therefore unhelpful.
Background
This is an updated version of the Cochrane Review previously published in 2018.
Epilepsy is a common neurological disorder characterised by recurrent seizures. Most people with epilepsy ...have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug‐resistant epilepsy, especially people with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add‐on treatment for drug‐resistant focal epilepsy.
Objectives
To evaluate the efficacy and tolerability of gabapentin when used as an add‐on treatment for people with drug‐resistant focal epilepsy.
Search methods
For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 11 August 2020. CRS Web includes randomised or quasi‐randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy. We imposed no language restrictions.
Selection criteria
Randomised, placebo‐controlled, double‐blind, add‐on trials of gabapentin in people with drug‐resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin.
Data collection and analysis
Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention‐to‐treat. We also undertook sensitivity best‐case and worst‐case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose‐response in regression models.
Main results
We identified no new studies for this update, therefore, the results and conclusions are unchanged.
In the previous update of this review, we combined data from six trials in meta‐analyses of 1206 randomised participants. The overall risk ratio (RR) for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 studies, 1206 participants; moderate‐certainty evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (95% CI 19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (95% CI 8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate‐certainty evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low‐certainty evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate‐certainty evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low‐certainty evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate‐certainty evidence). There was no evidence of a difference for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate‐certainty evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate‐certainty evidence). Overall, the studies were at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall certainty of the evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide CIs.
Authors' conclusions
Gabapentin has efficacy as an add‐on treatment in people with drug‐resistant focal epilepsy, and seems to be fairly well‐tolerated. However, the trials reviewed were of relatively short duration and provide no evidence for the long‐term efficacy of gabapentin beyond a three‐month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types. Further trials are needed to assess the long‐term effects of gabapentin, and to compare gabapentin with other add‐on drugs.
Summary
Purpose: Vigabatrin is an efficacious antiepileptic drug licensed as add‐on therapy in refractory epilepsy and used in infantile spasms. Eight years after licensing, there emerged a strong ...and possibly causative association with bilateral visual field loss. We report a systematic review ascertaining the magnitude of risk of vigabatrin associated visual field loss (VAVFL) and any clinical predictors of risk.
Methods: Electronic searches, including MEDLINE (1966–2009), EMBASE (1974–2009), and CINAHL (1982–2009), were conducted. Reports, published in full, of observational studies investigating the prevalence of visual field loss in patients with partial epilepsy treated with vigabatrin were included. Outcomes were the proportion with visual field loss, and the relative risk of VAVFL compared to similar nonexposed patients with epilepsy.
Key Findings: Thirty‐two studies were identified, which included 1,678 patients exposed to vigabatrin and 406 controls. Of the 1,678 exposed patients, 738 (44%) had visual field loss compared to just 30 (7%) among the 406 controls. The random‐effects estimate for the proportion of adults with visual field loss was 52% 95% confidence interval (CI) 46–59. The estimate for children was lower at 34% (95% CI 25–42). The relative risk for field loss in vigabatrin‐exposed patients was 4.0 (95% CI 2.9–5.5). Larger mean cumulative dose of vigabatrin and increasing age were associated with a higher proportion of patients with visual field loss.
Significance: Vigabatrin should be reserved for patients with epilepsy for whom there is no other alternative or for patients who have determined the benefit of ongoing treatment to outweigh the risk of VAVFL.
Postal self-completion questionnaires offer one of the least expensive modes of collecting patient based outcomes in health care research. The purpose of this review is to assess the efficacy of ...methods of increasing response to postal questionnaires in health care studies on patient populations.
The following databases were searched: Medline, Embase, CENTRAL, CDSR, PsycINFO, NRR and ZETOC. Reference lists of relevant reviews and relevant journals were hand searched. Inclusion criteria were randomised trials of strategies to improve questionnaire response in health care research on patient populations. Response rate was defined as the percentage of questionnaires returned after all follow-up efforts. Study quality was assessed by two independent reviewers. The Mantel-Haenszel method was used to calculate the pooled odds ratios.
Thirteen studies reporting fifteen trials were included. Implementation of reminder letters and telephone contact had the most significant effect on response rates (odds ratio 3.7, 95% confidence interval 2.30 to 5.97 p = or <0.00001). Shorter questionnaires also improved response rates to a lesser degree (odds ratio 1.4, 95% confidence interval 1.19 to 1.54). No evidence was found that incentives, re-ordering of questions or including an information brochure with the questionnaire confer any additional advantage.
Implementing repeat mailing strategies and/or telephone reminders may improve response to postal questionnaires in health care research. Making the questionnaire shorter may also improve response rates. There is a lack of evidence to suggest that incentives are useful. In the context of health care research all strategies to improve response to postal questionnaires require further evaluation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most investigations of savant skills in autism are based on individual case reports. The present study investigated rates and types of savant skills in 137 individuals with autism (mean age 24 ...years). Intellectual ability ranged from severe intellectual impairment to superior functioning. Savant skills were judged from parental reports and specified as 'an outstanding skill/knowledge clearly above participant's general level of ability and above the population norm'. A comparable definition of exceptional cognitive skills was applied to Wechsler test scores-requiring a subtest score at least 1 standard deviation above general population norms and 2 standard deviations above the participant's own mean subtest score. Thirty-nine participants (28.5%) met criteria for either a savant skill or an exceptional cognitive skill: 15 for an outstanding cognitive skill (most commonly block design); 16 for a savant skill based on parental report (mostly mathematical/calculating abilities); 8 met criteria for both a cognitive and parental rated savant skill. One-third of males showed some form of outstanding ability compared with 19 per cent of females. No individual with a non-verbal IQ below 50 met criteria for a savant skill and, contrary to some earlier hypotheses, there was no indication that individuals with higher rates of stereotyped behaviours/interests were more likely to demonstrate savant skills.
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