The authors reply: In response to Stanford et al.: after the exclusion of patients receiving insulin, the median gestational weight gain among the women in our study was lower in the metformin group than in the placebo group (4.6 kg [interquartile range, 1.3 to 7.2] vs. 6.3 kg [interquartile range, 2.9 to 9.2], P<0.001). In an evaluation of changes in postpartum weight from the initial antenatal visit, the median gestational weight loss was higher in the metformin group than in the placebo group (1.9 kg [interquartile range, −5.1 to 0.2] vs. 0 kg [interquartile range, −3.9 to 1.5], P = 0.02). We agree that metformin might reduce the risk of long-term obesity in these women.In response to Sahin and Corapcioglu: the American Diabetes Association classifies metformin as a category B drug (i.e., no evidence of risk in humans) during pregnancy. In the United Kingdom, metformin is recommended by the National Institute for Health and Care Excellence.1 There is no evidence of an increase in congenital malformations (including testicular abnormalities or defects in growth or motor development) in babies born to mothers treated with metformin.2,3 Blood-pressure results in a large cohort of 2-year-old children showed no differences between those whose mothers had received insulin and those whose mothers had received metformin. 4 Active B 12 (holotranscobalamin) and methylmalonic acid are better measures of vitamin B 12 status than are serum levels and do not appear to be pathologically altered in patients with type 2 diabetes after metformin treatment. DOI: 10.1056/NEJMc1603067Transient Smartphone "Blindness" To the Editor: Transient monocular vision loss is a common clinical presentation, and the cause is not always thromboembolic.1 We present two cases in which careful history taking established a benign cause (for the case histories, see the Supplementary Appendix, available with the full text of this letter at NEJM.org).A 22-year-old woman presented with a several months' history of recurrent impaired vision in the right eye that occurred at night. The results of ophthalmic and cardiovascular examinations were normal. Vitamin A levels and the results of magnetic resonance angiography, echocardiography, and a thrombophilia screening were also normal.The second case involved a 40-year-old woman who presented with a 6-month history of recurrent monocular visual impairment on waking, lasting up to 15 minutes. The results of investigations for a vascular cause were again normal. Aspirin therapy had been commenced. When the patients were seen in our neuroophthalmic clinic, detailed history taking revealed that symptoms occurred only after several minutes of viewing a smartphone screen, in the dark, while lying in bed (before going to sleep in the first case and after waking in the second). Both patients were asked to experiment and record their symptoms. They reported that the symptoms were always in the eye contralateral to the side on which the patient was lying.We hypothesized that the symptoms were dueThe New England ...

ObjectiveAccurate preoperative predictions of seizure freedom following surgery for focal drug resistant epilepsy remain elusive. Our objective was to systematically evaluate all meta-analyses of epilepsy surgery with seizure freedom as the primary outcome, to identify clinical features that are consistently prognostic and should be included in the future models.MethodsWe searched PubMed and Cochrane using free-text and Medical Subject Heading (MeSH) terms according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This study was registered on PROSPERO. We classified features as prognostic, non-prognostic and uncertain and into seven subcategories: ‘clinical’, ‘imaging’, ‘neurophysiology’, ‘multimodal concordance’, ‘genetic’, ‘surgical technique’ and ‘pathology’. We propose a structural causal model based on these features.ResultsWe found 46 features from 38 meta-analyses over 22 years. The following were consistently prognostic across meta-analyses: febrile convulsions, hippocampal sclerosis, focal abnormal MRI, Single-Photon Emission Computed Tomography (SPECT) coregistered to MRI, focal ictal/interictal EEG, EEG-MRI concordance, temporal lobe resections, complete excision, histopathological lesions, tumours and focal cortical dysplasia type IIb. Severe learning disability was predictive of poor prognosis. Others, including sex and side of resection, were non-prognostic. There were limited meta-analyses investigating genetic contributions, structural connectivity or multimodal concordance and few adjusted for known confounders or performed corrections for multiple comparisons.SignificanceSeizure-free outcomes have not improved over decades of epilepsy surgery and despite a multitude of models, none prognosticate accurately. Our list of multimodal population-invariant prognostic features and proposed structural causal model may serve as an objective foundation for statistical adjustments of plausible confounders for use in high-dimensional models.PROSPERO registration numberCRD42021185232.

Objectives: One-third of individuals with focal epilepsy do not achieve seizure freedom despite best medical therapy. Mesial temporal lobe epilepsy (MTLE) is the most common form of drug resistant focal epilepsy. Surgery may lead to long-term seizure remission if the epileptogenic zone can be defined and safely removed or disconnected. We compare published outcomes following open surgical techniques, radiosurgery (SRS), laser interstitial thermal therapy (LITT) and radiofrequency ablation (RF-TC).Methods: PRISMA systematic review was performed through structured searches of PubMed, Embase and Cochrane databases. Inclusion criteria encompassed studies of MTLE reporting seizure-free outcomes in ≥10 patients with ≥12 months follow-up. Due to variability in open surgical approaches, only comparative studies were included to minimize the risk of bias. Random effects meta-analysis was performed to calculate effects sizes and a pooled estimate of the probability of seizure freedom per person-year. A mixed effects linear regression model was performed to compare effect sizes between interventions.Results: From 1,801 screened articles, 41 articles were included in the quantitative analysis. Open surgery included anterior temporal lobe resection as well as transcortical and trans-sylvian selective amygdalohippocampectomy. The pooled seizure-free rate per person-year was 0.72 (95% CI 0.66–0.79) with trans-sylvian selective amygdalohippocampectomy, 0.59 (95% CI 0.53–0.65) with LITT, 0.70 (95% CI 0.64–0.77) with anterior temporal lobe resection, 0.60 (95% CI 0.49–0.73) with transcortical selective amygdalohippocampectomy, 0.38 (95% CI 0.14–1.00) with RF-TC and 0.50 (95% CI 0.34–0.73) with SRS. Follow up duration and study sizes were limited with LITT and RF-TC. A mixed-effects linear regression model suggests significant differences between interventions, with LITT, ATLR and SAH demonstrating the largest effects estimates and RF-TC the lowest.Conclusions: Overall, novel “minimally invasive” approaches are still comparatively less efficacious than open surgery. LITT shows promising seizure effectiveness, however follow-up durations are shorter for minimally invasive approaches so the durability of the outcomes cannot yet be assessed. Secondary outcome measures such as Neurological complications, neuropsychological outcome and interventional morbidity are poorly reported but are important considerations when deciding on first-line treatments.