Ofatumumab and high-dose methylprednisolone for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia.

Ofatumumab is a humanized anti-CD20 monoclonal antibody that has been approved by the FDA for the treatment of patients with chronic lymphocytic leukemia. We conducted a phase II single-arm study at a single center. Patients received ofatumumab (300 mg then 1000 mg weekly for 12 weeks) and methylprednisolone (1000 mg/m(2) for 3 days of each 28-day cycle). Twenty-one patients enrolled, including 29% with unfavorable cytogenetics (del17p or del11q). Ninety percent of patients received the full course without dose reductions or delays. The overall response rate was 81% (17/21) with 5% complete response, 10% nodular partial response, 67% partial response, 14% stable disease and 5% progressive disease. After a median follow-up of 31 months, the median progression-free survival was 9.9 months and the median time to next treatment was 12.1 months. The median overall survival has not yet been reached. The combination of high-dose methylprednisolone and ofatumumab is an effective and tolerable treatment regimen. This regimen may be useful for patients who are unable to tolerate more aggressive therapies, or have not responded to other treatments

Perceptions of exclusive breastfeeding among Bidayuh mothers in Sarawak, Malaysia: a qualitative study

Despite its benefits, exclusive breast feeding is not widely practised in Malaysia. As the decision for exclusive breastfeeding is influenced by social and cultural context, it is important to conduct studies in different societies in Malaysia. This qualitative study aimed to explore the perceptions of exclusive breastfeeding among Bidayuh women in Sarawak, Malaysia. Methods: A purposive sample of Bidayuh women who exclusively breastfed their infants for at least three months were recruited from one rural village in one sub-district of Kuching. An in-depth interview asked participants to respond to an open-ended questionnaire designed to elicit perception/challenges and motivating factors to continue exclusive breastfeeding. Results: Participants believed that it was their responsibility to breastfeed and breast milk was regarded as a gift from God with goodness that brought a proud and joyful experience. Breastfeeding also strengthened the mother-infant's physical and emotional bonding. Social support was important to ensure the continuation of exclusive breast feeding. Conclusion: Health care workers should emphasise these perceptions in their teaching and continue to provide support for exclusive breast feeding. More studies in other ethnic groups in Malaysia are recommended so as to provide relevant content for health care professionals to frame health education and promotion of exclusive breastfeeding within a culturally meaningful context

Impurity effects on charge transport and magnetoconductance in a single layer poly(3-hexyl-thiophene) device

received: 2016-01-10 accepted: 2016-05-05 published: 2016-05-17The work was supported by the China Scholarship Council and Engineering (HG, SC, HL, TZ, JH), National Science Foundation of China, 61574095, and Physical Sciences Research Council Grant Nos. EP/J50029X/1, EP/K004484/1, and EP/L020114/1

Lower lid entropion secondary to treatment with alpha-1a receptor antagonist: a case report

<p>Abstract</p> <p>Introduction</p> <p>The use of alpha-1a receptor antagonists (tamsulosin) is widely accepted in the treatment of benign prostatic hypertrophy (BPH). It has previously been implicated as a causative agent in intra-operative floppy iris syndrome due to its effects on the smooth muscle. We report a case of lower lid entropion that may be related to a patient commencing treatment of tamsulosin.</p> <p>Case presentation</p> <p>A 74-year-old Caucasian man was started on alpha 1-a receptor antagonist (Tamsulosin) treatment for benign prostatic hypertrophy. Eight days later, he presented to the ophthalmology unit with a right lower lid entropion which was successfully treated surgically with a Weiss procedure.</p> <p>Conclusion</p> <p>We report a case of lower lid entropion that may be secondary to the recent use of an alpha-1a blocker (tamsulosin). This can be explained by considering the effect of autonomic blockade on alpha-1 receptors in the Muller's muscle on a patient that may already have an anatomical predisposition to entropion formation due to a further reduction in muscle tone.</p

A one-year trial of lamivudine for chronic hepatitis B

Background and Methods: In preliminary trials, lamivudine, an oral nucleoside analogue, has shown promise for the treatment of chronic hepatitis B. We conducted a one-year double-blind trial of lamivudine in 358 Chinese patients with chronic hepatitis B. The patients were randomly assigned to receive 25 mg of lamivudine (142 patients), 100 mg of lamivudine (143), or placebo (73) orally once daily. The patients underwent liver biopsies before entering the study and after completing the assigned treatment regimen. The primary end point was a reduction of at least two points in the Knodell necroinflammatory score. Results: Hepatic necroinflammatory activity improved by two points or more in 56 percent of the patients receiving 100 mg of lamivudine, 49 percent of those receiving 25 mg of lamivudine, and 25 percent of those receiving placebo (P<0.001 and P=0.001, respectively, for the comparisons of lamivudine treatment with placebo). Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg of lamivudine, 8 percent of those receiving 25 mg, and 26 percent of those receiving placebo. The 100mg dose of lamivudine was associated with a reduced progression of fibrosis (P=0.01 for the comparison with placebo) and with the highest rate of hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg, development of antibody to HBeAg, and undetectable HBV DNA) (16 percent), the greatest suppression of HBV DNA (98 percent reduction at week 52 as compared with the base-line value), and the highest rate of sustained normalization of alanine aminotransferase levels (72 percent). Ninety-six percent of the patients completed the study. The incidence of adverse events was similar in all groups, and there were few serious events. Conclusions: In a one-year study, lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg.published_or_final_versio

Greater incidence of depression with hypnotic use than with placebo

Abstract Background Although it has been claimed that insomnia causes an increased risk for depression, adequate controlled trials testing this hypothesis have not been available. This study contrasted the incidence of depression among subjects receiving hypnotics in randomized controlled trials versus those receiving placebo. Methods The incidence of depression among patients randomized to hypnotic drugs or placebo was compiled from prescribing information approved by the United States Food and Drug Administration (FDA) and from FDA New Drug Application documents. Available data for zolpidem, zaleplon, eszopiclone, and ramelteon were accessed. Results Data for 5535 patients randomized to a hypnotic and for 2318 randomized to placebo were compiled. The incidence of depression was 2.0% among participants randomized to hypnotics as compared to 0.9% among those randomized in parallel to placebo (p Conclusion Modern hypnotics were associated with an increased incidence of depression in data released by the FDA. This suggests that when there is a risk of depression, hypnotics may be contra-indicated. Preventive treatments such as antidepressant drugs, cognitive-behavioral therapy, or bright light might be preferred. Limitations in the FDA data prevented a formal meta-analysis, and there was a lack of information about drop-out rates and definitions of depression. Trials specifically designed to detect incident depression when treating insomnia with hypnotic drugs and better summarization of adverse events in trials submitted to the FDA are both necessary.</p

Impediments to eye transplantation: Ocular viability following optic-nerve transection or enucleation

Maintenance of ocular viability is one of the major impediments to successful whole-eye transplantation. This review provides a comprehensive understanding of the current literature to help guide future studies in order to overcome this hurdle. A systematic multistage review of published literature was performed. Three specific questions were addressed: (1) Is recovery of visual function following eye transplantation greater in cold-blooded vertebrates when compared with mammals? (2) Is outer retina function following enucleation and reperfusion improved compared with enucleation alone? (3) Following optic-nerve transection, is there a correlation between retinal ganglion cell (RGC) survival and either time after transection or proximity of the transection to the globe? In a majority of the studies performed in the literature, recovery of visual function can occur after whole-eye transplantation in cold-blooded vertebrates. Following enucleation (and reperfusion), outer retinal function is maintained from 4 to 9 h. RGC survival following optic-nerve transection is inversely related to both the time since transection and the proximity of transection to the globe. Lastly, neurotrophins can increase RGC survival following optic-nerve transection. This review of the literature suggests that the use of a donor eye is feasible for whole-eye transplantation.published_or_final_versio

Rewritable nanoscale oxide photodetector

Nanophotonic devices seek to generate, guide, and/or detect light using structures whose nanoscale dimensions are closely tied to their functionality. Semiconducting nanowires, grown with tailored optoelectronic properties, have been successfully placed into devices for a variety of applications. However, the integration of photonic nanostructures with electronic circuitry has always been one of the most challenging aspects of device development. Here we report the development of rewritable nanoscale photodetectors created at the interface between LaAlO3 and SrTiO3. Nanowire junctions with characteristic dimensions 2-3 nm are created using a reversible AFM writing technique. These nanoscale devices exhibit a remarkably high gain for their size, in part because of the large electric fields produced in the gap region. The photoconductive response is gate-tunable and spans the visible-to-near-infrared regime. The ability to integrate rewritable nanoscale photodetectors with nanowires and transistors in a single materials platform foreshadows new families of integrated optoelectronic devices and applications.Comment: 5 pages, 5 figures. Supplementary Information 7 pages, 9 figure

Outcomes with ibrutinib by line of therapy and post‐ibrutinib discontinuation in patients with chronic lymphocytic leukemia: Phase 3 analysis

The efficacy of ibrutinib has been demonstrated in patients with chronic lymphocytic leukemia (CLL), including as first‐line therapy. However, outcomes after ibrutinib discontinuation have previously been limited to higher‐risk populations with relapsed/refractory (R/R) disease. The objective of this study was to evaluate outcomes of ibrutinib‐treated patients based on prior lines of therapy, including after ibrutinib discontinuation. Data were analyzed from two multicenter phase 3 studies of single‐agent ibrutinib: RESONATE (PCYC‐1112) in patients with R/R CLL and RESONATE‐2 (PCYC‐1115) in patients with treatment‐naive (TN) CLL without del(17p). This integrated analysis included 271 ibrutinib‐treated non‐del(17p) patients with CLL (136 TN and 135 R/R). Median progression‐free survival (PFS) was not reached for subgroups with 0 and 1/2 prior therapies but was 40.6 months for patients with ≥3 therapies (median follow‐up: TN, 36 months; R/R, 44 months). Median overall survival (OS) was not reached in any subgroup. Overall response rate (ORR) was 92% in TN and 92% in R/R, with depth of response increasing over time. Adverse events (AEs) and ibrutinib discontinuation due to AEs were similar between patient groups. Most patients (64%) remain on treatment. OS following discontinuation was 9.3 months in R/R patients (median follow‐up 18 months, n = 51) and was not reached in TN patients (median follow‐up 10 months, n = 30). In this integrated analysis, ibrutinib was associated with favorable PFS and OS, and high ORR regardless of prior therapies in patients with CLL. The best outcomes following ibrutinib discontinuation were for patients receiving ibrutinib in earlier lines of therapy