A 24-week study to evaluate the efficacy and safety of once-weekly dulaglutide added on to glimepiride in type 2 diabetes (AWARD-8).

AIMS: To evaluate the safety and efficacy of once-weekly dulaglutide 1.5 mg, a long-acting glucagon-like peptide-1 receptor agonist, compared with placebo in patients with type 2 diabetes (T2D) on glimepiride monotherapy. METHODS: This phase III, randomized (4 : 1; dulaglutide:placebo), double-blind, placebo-controlled, 24-week study compared the safety and efficacy of once-weekly dulaglutide 1.5 mg with placebo in sulphonylurea-treated (≥half-maximal dose, stable ≥3 months) patients (N = 300) with T2D and inadequate glycaemic control [glycated haemoglobin (HbA1c) ≥7.5 and ≤9.5% (≥58 mmol/mol and ≤80 mmol/mol)]. Analysis was carried out according to intention-to-treat. RESULTS: At baseline, the mean participant age was 58 years; mean HbA1c was 8.4% (68 mmol/mol) and mean weight was 85.5 kg. Dulaglutide 1.5 mg was superior to placebo at 24 weeks for HbA1c reduction from baseline with a between-group HbA1c difference of -1.3% [95% confidence interval (CI) -1.6, -1.0] or -14 mmol/mol (95% CI -17, -11); p < 0.001. A greater proportion of participants in the dulaglutide group reached an HbA1c level of <7.0% (53 mmol/mol) compared with placebo (55.3% vs 18.9%; p < 0.001). Dulaglutide significantly decreased fasting serum glucose from baseline compared with placebo (between-group difference -1.86 mmol/l (95% CI -2.58, -1.14) or -33.54 mg/dl (95% CI -46.55, -20.53); p < 0.001. Weight was decreased significantly from baseline in the dulaglutide group (p < 0.001); the between-group difference was not significant. The most common treatment-emergent adverse events for dulaglutide 1.5 mg were gastrointestinal: nausea (10.5%), diarrhoea (8.4%) and eructation (5.9%). Total hypoglycaemia was higher with dulaglutide 1.5 mg vs placebo (2.37 and 0.07 events/participant/year, respectively; p = 0.025). No severe hypoglycaemia was reported. CONCLUSIONS: Once-weekly dulaglutide 1.5 mg had a favourable benefit/risk profile when added to glimepiride monotherapy.

The Cole relaxation frequency as a parameter to identify cancer in breast tissue.

PURPOSE: To correlate the Cole relaxation frequencies obtained from measurements of the electrical properties of breast tissue to the presence or absence of cancer. METHODS: Four-lead impedance measurements were obtained on ex vivo specimens extracted during surgery from 187 volunteer patients. Data were acquired with a commercial Solartron impedance bridge employing 4-lead Ag-AgCl or blackened platinum (BPt) electrodes at frequencies logarithmically spaced from 1 Hz to 3.2 × 10(7) Hz utilizing 6-10 frequencies per decade. The Cole frequencies obtained from these measurements were correlated with the tissue health status (cancer or noncancer) obtained from histological analysis of the specimens. RESULTS: Analysis of the impedance measurements showed that the Cole relaxation frequencies correlated to the presence or absence of cancer in the examined tissue with a sensitivity up to 100% (95% CI, 99%-100%) and a specificity up to 85% (95% CI, 79%-91%) based on the ROC curve of the data with the Cole frequency as the classifier. CONCLUSIONS: The results show that the Cole frequency alone is a viable classifier for malignant breast anomalies. Results of the current work are consistent with recent bioimpedance measurements on single cell and cell suspension breast cell lines.

Physiologic responses to racial rejection images among young adults from African-American backgrounds.

Physiologic reactivity to racially rejecting images was assessed in 35 young adults (10 males, 25 female) from African-American backgrounds using the startle probe paradigm. In a laboratory setting, participants viewed 16 images depicting racial rejection, racial acceptance, nonracial negative, and nonracial positive themes. While viewing these images, startling bursts of noise were presented and the magnitude of the eyeblink responses were measured. Results supported an attentional mechanism which suggests that, while viewing both racially rejecting and nonracial positive images, individuals may be so absorbed in processing the images that they appear less distracted by the startling noise. However, these patterns were only found for participants low in racial regard. Young adults who felt positively about their racial background did not exhibit differential processing of startle stimuli as a function of slide themes. Race-rejection sensitivity did not moderate startle reactivity. Developmental implications, particularly in light of coping with racial discrimination, are discussed.

Preoperative chemotherapy and radiation therapy for patients with cancer of the esophagus: a potentially curative approach.

Twenty-one patients with squamous cell cancer of the esophagus were entered into a pilot clinical trial using preoperative chemotherapy (5-fluorouracil and cis-platinum) and radiation with the intent of improving cure rate and survival. After the preoperative treatment was complete, 15 patients (71%) were resected for cure. Seven (47%) of 15 had no histologic evidence of cancer in the resected esophagus, but two of these had microscopic cancer in resected lymph nodes. The median survival for all patients entered in the trial was 18 months, whereas for those with no cancer in the resected esophagus the median survival was 24 months. The six patients who either refused surgery (two patients) or were unresectable at surgery (four patients) died within nine months. Our conclusion in this trial is that survival and potential cure are clearly linked to successfully clearing the esophagus and nodes of histologic evidence of tumor through preoperative treatment.

Ophthalmic drug delivery systems.

In recent years, increased attention has been given to the development of new systems for the delivery of ophthalmic medication. These systems are of interest for several reasons: they generally require less frequent administration than eyedrops; some of them provide therapy with fewer drug side effects than eyedrops; and they can offer practical advantages in situations where repeated, self-medication by patients is not feasible. Further, by providing continuous delivery, they allow the use of some newly emerging drugs that have very short biological half-lives. Some ocular delivery systems extend the duration of drug action by enhancement of corneal absorption; these include soluble gels and emulsions, hydrophilic ocular inserts, ion-pair associations, pro-drugs, and liposomes. Other delivery systems provide for a controlled release of drugs, thus avoiding the pulse-entry with which side-effects are associated. These systems can be based on any of several different mechanisms, and include both erodible and nonerodible matrices. The various new systems that have been developed, or are known to be under development, are described in this review, along with their mechanisms and limitations, and with the therapeutic rationale for their use.

Pharmacokinetics of topically applied ophthalmic drugs.

Pharmacokinetic applications in recent years have led to significant advances in systemic drug therapy, but applications to topical, ophthalmic therapy have been far less numerous. Pharmacokinetics is the study of the time course of the absorption, distribution, metabolism, and elimination of an administered drug. Thus, it includes the quantitation of such elements of drug bioavailability as tear dilution, drug binding, and vehicle effects; factors affecting corneal absorption and subsequent tissue distribution; dosage form effects; and pathways of elimination. These factors are important because they significantly influence the clinical responses to administered drugs, in some instances to a profound degree. These elements and their clinical implications are discussed along with some recent applications, exemplified with data from studies on frequently prescribed drugs.

Lithium in hospitalized aggressive children with conduct disorder: a double-blind and placebo-controlled study.

OBJECTIVE: To assess critically the efficacy and safety of lithium and replicate earlier findings in a larger sample of aggressive children with conduct disorder and to assess the utility of the Profile of Mood States (POMS) in this population. METHODS: Children hospitalized for treatment-refractory severe aggressiveness and explosiveness and with diagnosed conduct disorder were subjects in this double-blind, placebo-controlled clinical trial. After a 2-week placebo baseline period, children were randomly assigned to lithium or placebo treatment for 6 weeks of placebo. The main outcome measures were the Global Clinical Judgments (Consensus) Scale, Children's Psychiatric Rating Scale, Conners Teacher Questionnaire, Parent-Teacher Questionnaire, and the POMS. RESULTS: Fifty children (mean age 9.4 years) completed this study. The mean optimal daily dose of lithium was 1,248 mg and the mean serum level was 1.12 mEq/L. Lithium was superior to placebo, although the effects on some measures were more modest than in a previous study. CONCLUSIONS: Lithium appears to be an effective treatment for some severely aggressive children with conduct disorder. Although the POMS appeared to be reliable, it did not detect any response to lithium.

The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children.

This double-blind and placebo-controlled clinical trial in autistic children had three objectives: (a) to replicate earlier findings that haloperidol administration is associated with a significant reduction of behavioral symptoms; (b) to further assess its safety when given on a short-term basis; and (c) to assess whether it has an effect on discrimination learning. Forty-five children, 2.02 to 7.58 years old (M = 4.49), completed this crossover design, with random assignment to treatment sequences. Haloperidol was shown to be a powerful therapeutic agent when administered for 4 weeks and free of side effects; at doses ranging from 0.25 to 4.0 mg/day (M = 0.844), there was a clinically and statistically significant reduction of a variety of symptoms. Under the given conditions, the children failed to learn on either haloperidol or placebo.

Sexuality and the older person with cancer.

PURPOSE/OBJECTIVES: To review the particular needs of older patients with cancer with respect to sexuality and to present appropriate nursing strategies to facilitate adjustment. DATA SOURCES: Books, journals, and American Cancer Society publications. DATA SYNTHESIS: Physical and emotional changes caused by diagnosis and treatment of cancer often are compounded in the older patient. Of particular concern is sexual adjustment, which already may be compromised by the effects of aging on normal sexual functioning, absence of a partner, or personal/societal prohibitions against sexuality in this population. CONCLUSIONS: Exercise, nutrition, and self-esteem intervention programs, coupled with strategies to facilitate sexual activity that take into account normal aging, can help older patients with cancer to reestablish usual sexual functioning. IMPLICATIONS FOR NURSING PRACTICE: Nurses must establish a comfort level with sexual assessment and patient intervention so that they can provide counseling and suggest appropriate interventions.

The cancer amputee and sexuality.

To the person experiencing amputation, the loss of a limb has a serious psychosexual impact. Whatever the age, the surgical procedure itself, pain, deformity, inability to perform simple customary acts, economic threat, and many other problems impose on the person facing the loss of their limb. Commonly, concentration is focused on functional abilities during and after prosthetic rehabilitation, and care taken to preserve the person's sexuality is often omitted. Major limb amputation can cause a decrease in self-esteem and body image due to perceived mutation, and this in turn can create emotional hurdles for both the patient and partner. Several potential problems such as the mechanics of body positioning during sex play, balance and movement, and phantom pain sensations can alter sexual function. Added difficulties include chemotherapy-induced neuropathies and enforced isolation because of limited mobility. Although these various disabling maladies may require alterations in a sexual relationship, sex drive and desire usually remain intact. Specific assessment techniques and interventions must be made available to enable the nurse to discuss sexual concerns at all stages of cancer and its treatment. As well, we must not fail to see alternatives to stereotypical behavior and acknowledge each patient's unique sexual identify.