Seizure recurrence and remission after switching antiepileptic drugs

Purpose: Studies of seizure outcome in patients undergoing serial antiepileptic drug trials have all been uncontrolled, with no account made for the spontaneous changes in disease state that could confound the elucidation of drug effects. In addition, no study has ever looked at outcome following antiepileptic drug switch in seizure‐free patients, despite the fact that this is done routinely in clinical practice. We aimed to address both of these issues using a matched case‐cohort design. Methods: We followed patients taking phenytoin or carbamazepine in monotherapy for focal epilepsy who were being crossed over to a newer agent as part of studies on the metabolic effects of anticonvulsant therapy. Many had been seizure‐free but were being switched nonetheless due to side effects or concerns about long‐term adverse consequences. Each patient was matched with two controls of the same seizure status who were taking anticonvulsant monotherapy and whose drug was not switched. Seizure freedom over the ensuing 6 months was the primary end point. Key Findings: There were 43 cases and 86 matched controls. Twenty‐three patients (cases) had been seizure‐free on their old drug; 5 (21.7%) had seizure recurrence after drug switch compared to 2 (4.3%) of 46 matched controls. Twenty patients (cases) were having seizures on their old drug; 6 (30%) entered remission after drug switch, compared to 8 of 40 matched controls (20%). The two groups differed at baseline in number of anticonvulsants previously failed, which was the most important factor for prognosis. After statistical adjustment to account for this, seizure‐free patients had 6.53 times higher odds of seizure recurrence if switched to a new drug (95% confidence interval [CI] 1.02–61.19; p = 0.06). Non–seizure‐free patients had 1.66 times higher odds of remission if they remained on the same drug compared to switching, although this was not significant (95% CI 0.36–8.42; p = 0.532). Neither dose changes, nor drug mechanism, nor duration of seizure freedom had any bearing upon the results. Significance: Although the large majority of seizure‐free patients remain so when switched to another agent, about one sixth have a recurrence attributable to the change. Conversely, our study design provides the first evidence to suggest that most improvements in drug‐resistant patients are likely due to spontaneous remissions, not new drug introductions. These findings have conflicting implications for two competing models of comparative antiepileptic drug efficacy, which will require further study to elaborate.     

Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells

Evidence has accumulated to suggest that magnesium might play a role in controlling angiogenesis. Since microvascular endothelial cells are protagonists in this process, we investigated the behavior of these cells cultured in low extracellular magnesium or silenced for its transporter Transient Receptor Potential Melastatin (TRPM)7, essential for cellular magnesium homeostasis. In particular, we focused on some crucial steps of the angiogenic process, i.e. proliferation, migration, protease production and organization in tridimensional structures. Silencing TRPM7 mimics the effects of low extracellular magnesium on human microvascular endothelial cells (HMEC). Indeed, while no effects were observed on the production of metalloproteases and on tridimensional organization on matrigel, both magnesium deficiency and silencing of TRPM7 impair cell migration and inhibit growth by arresting the cells in the G0/G1 and G2/M phases of the cell cycle. Since low extracellular magnesium markedly decreases TRPM7 in HMEC, we suggest that TRPM7 downregulation might mediate low magnesium-induced inhibition of cell growth and migration. Human endothelial cells from the umbilical vein are growth inhibited by low magnesium and growth stimulated after TRPM7 silencing. An impairment of ERK phosphorylation in HMEC silencing TRPM7 is responsible, in part, for the different proliferative behavior of these two cell types. We broadened our studies also to endothelial colony-forming cells and found that they are sensitive to fluctuations of the concentrations of extracellular magnesium, while their proliferation rate is not modulated by TRPM7 silencing. Our results point to magnesium and TRPM7 as a modulators of the angiogenic phenotype of microvascular endothelial cells.     

Young Adults at Risk for Excess Alcohol Consumption Are Often Not Asked or Counseled About Drinking Alcohol

Background  

Excessive alcohol consumption is most widespread among young adults. Practice guidelines recommend screening and physician advice, which could help address this common cause of injury and premature death.     

Combination of low doses of Enzastaurin and Lenalidomide has synergistic activity in B-non-Hodgkin lymphoma cell lines

Less toxic and more active treatments are needed for indolent lymphomas as there is no curative treatment, and patients eventually die due to complications related to their disease. The purpose of the present study was to assess the antitumour activity of the combination of low doses of Enzastaurin and Lenalidomide (Revlimid) on B-lymphoma cell lines. The combination of Enzastaurin and Lenalidomide, at doses as low as 1 μM, showed strong synergism against indolent lymphomas by reducing cell growth, producing an increase in G0-G1 phase followed by significant decrease in S phase, increasing apoptosis, and inhibiting PI3K/AKT, PKC and MAPK/ERK pathways. These preclinical findings, together with promising results obtained with Lenalidomide for the treatment of non-Hodgkin lymphoma, suggest that further evaluation of the combination of Enzastaurin and Lenalidomide for the treatment of indolent lymphomas is warranted. These compounds, with a favourable toxicity profile, are not classic chemotherapeutic agents, causing severe side effects, and could be considered an example of a new innovative attempt of an anti-cancer 'soft treatment'.     

Can the rural poor in India afford to treat non‐communicable diseases

Objective Non‐communicable diseases (NCD) are on the increase in low‐income countries, where healthcare costs are paid mostly out‐of‐pocket. We investigate the financial burden of NCD vs. communicable diseases (CD) among rural poor in India and assess whether they can afford to treat NCD. Methods We used data from two household surveys undertaken in 2009–2010 among 7389 rural poor households (39 205 individuals) in Odisha and Bihar. All persons from the sampled households, irrespective of age and gender, were included in the analysis. We classify self‐reported illnesses as NCD, CD or ‘other morbidities’ following the WHO classification. Results Non‐communicable diseases accounted for around 20% of the diseases in the month preceding the survey in Odisha and 30% in Bihar. The most prevalent NCD, representing the highest share in outpatient costs, were musculoskeletal, digestive and cardiovascular diseases. Cardiovascular and digestive problems also generated the highest inpatient costs. Women, older persons and less‐poor households reported higher prevalence of NCD. Outpatient costs (consultations, medicines, laboratory tests and imaging) represented a bigger share of income for NCD than for CD. Patients with NCD were more likely to report a hospitalisation. Conclusion Patients with NCD in rural poor settings in India pay considerably more than patients with CD. For NCD cases that are chronic, with recurring costs, this would be aggravated. The cost of NCD care consumes a big part of the per person share of household income, obliging patients with NCD to rely on informal intra‐family cross‐subsidisation. An alternative solution to finance NCD care for rural poor patients is needed.     

Femtosecond laser-assisted implantation of corneal stroma lenticule for keratoconus

International Ophthalmology - To review recent progress, challenges, and future perspectives of stromal keratophakia for the treatment of advanced keratoconus. We systematically reviewed the...