Adjunctive everolimus therapy in tuberous sclerosis-associated refractory epilepsy

Presentation In this article we are reporting the beneficial impact of everolimus treatment on the renal & CNS manifestations of TSC. Diagnosis The patient diagnosed with refractory seizure associated with tuberous sclerosis. Treatment The patient was treated with everolimus, and he was commenced at a dose of 10 mg daily. Conclusion This report shows that everolimus treatment for three years of refractory seizures in patients with TSC, can lead to a clinically meaningful reduction in seizure frequency. Compared with other anti-epileptic medications, everolimus demonstrated additional benefits in reducing Subependymal giant cell astrocytoma (SEGA) and renal angiomyolipoma volume. At the time of preparation of this report, the patient continue treatment with daily everolimus without adverse events.</div

Association of exposures to seated postures with immediate increases in back pain: A systematic review of studies with objectively measured sitting time

Objective: The purpose of this study was to conduct a systematic review of studies to determine whether sitting time measured objectively (by laboratory controlled time trial, direct observation, or wearable sensor) is associated with the immediate increase in low back pain (LBP) (determined by pain scale rating) in people >18 years of age. Methods: Four databases (PubMed, EMBASE, SPORTDiscus, and Cumulative Index to Nursing and Allied Health Literature) were searched from inception to September 1, 2018. Randomized controlled trials and cohort and cross-sectional studies, where objectively measured sitting time was temporally matched with a measure of LBP in adults, were included. Studies without a control session conducted on a separate day were excluded. Screening, full-text review, data extraction, and risk of bias assessment (Quality In Prognosis Studies) of included papers were performed independently by 2 reviewers, with a third available to resolve disagreements. Results: In total, 609 articles were identified, 361 titles/abstracts were screened,75 full-text articles were assessed for eligibility, and 10 met the inclusion criteria. All but 1 reported sitting time to be associated with an immediate increase in LBP. Six of these reported clinically relevant pain levels (n = 330). Half of the included studies were rated as having a low risk of bias and the remaining were rated as having a moderate risk of bias. Conclusion: Prolonged sitting increases immediate reporting of LBP in adults; however, no conclusion between sitting and clinical episodes of LBP can be made. Based upon these findings, we recommend that future prospective studies should match objectively measured sitting with temporally related pain measurements to determine whether prolonged sitting can trigger a clinical episode of LBP

Elevated preoperative heart rate is associated with cardiopulmonary and autonomic impairment in high-risk surgical patients

Background: Elevated preoperative heart rate (HR) is associated with perioperative myocardial injury and death. In apparently healthy individuals, high resting HR is associated with development of cardiac failure. Given that patients with overt cardiac failure have poor perioperative outcomes, we hypothesized that subclinical cardiac failure, identified by cardiopulmonary exercise testing, was associated with elevated preoperative HR > 87 beats min-1(HR > 87). Methods: This was a secondary analysis of an observational cohort study of surgical patients aged ≥45 yr. The exposure of interest was HR > 87, recorded at rest before preoperative cardiopulmonary exercise testing. The predefined outcome measures were the following established predictors of mortality in patients with overt cardiac failure in the general population: ventilatory equivalent for carbon dioxide (V E/V co2) ratio ≥34, heart rate recovery ≤6 and peak oxygen uptake (V o2) ≤14 ml kg-1min-1. We used logistic regression analysis to test for association between HR > 87 and markers of cardiac failure. We also examined the relationship between HR > 87 and preoperative left ventricular stroke volume in a separate cohort of patients. Results: HR > 87 was present in 399/1250 (32%) patients, of whom 438/1250 (35%) had V E/V co2ratio ≥34, 200/1250 (16%) had heart rate recovery ≤6, and 396/1250 (32%) had peak V o2≤14 ml kg-1min-1. HR > 87 was independently associated with peak V o2≤14 ml kg-1min-1{odds ratio (OR) 1.69 [1.12-3.55]; P=0.01} and heart rate recovery ≤6 (OR 2.02 [1.30-3.14]; P 87 was not associated with V E/V co2ratio ≥34 (OR 1.31 [0.92-1.87]; P=0.14). In a separate cohort, HR > 87 (33/181; 18.5%) was associated with impaired preoperative stroke volume (OR 3.21 [1.26-8.20]; P=0.01). Conclusions: Elevated preoperative heart rate is associated with impaired cardiopulmonary performance consistent with clinically unsuspected, subclinical cardiac failure. Clinical trial registration. ISRCTN88456378

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial

Background Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. Methods In this multicentre, open-label, randomised controlled trial, we recruited women aged 18–40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. Findings Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference −0·19%; 95% CI −0·34 to −0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). Interpretation Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use