Methods to determine the minimum important difference for a sexual event diary used by postmenopausal women with hypoactive sexual desire disorder

IntroductionRecently, there has been much discussion in the literature about how to determine the meaningfulness of results generated from a patient-reported outcome measure. A number of reviews have shown that there are two main approaches: anchor- and distribution-based approaches for determining the minimum important difference (MID) for a new measure. There are issues with calculating an MID using each method: Will the two approaches give the same estimate? If the estimates differ, how do you decide on one estimate? Would asking patients directly be more beneficial?AimA case study was presented to address these issues based on a newly developed diary assessing number of satisfactory sexual events (SSEs) per week in women with hypoactive sexual desire disorder (HSDD).MethodsAnchor- and distribution-based estimates were generated from data gathered in two double-blind, placebo-controlled, parallel group trials for the treatment of HSDD (N = 788). A novel interview study was used to ask women directly about an MID for SSEs (N = 77).Main Outcome MeasuresDefining the MID for an SSE diary in women with HSDD.ResultsThe estimates varied, producing a range of mean MID estimates between 0.04 and 0.46 SSEs per week.ConclusionsWe recommend that rather than defining the MID, a range should be selected from the set of estimates formed by the limits of the 95% confidence intervals. Symonds T, Spino C, Sisson M, Soni P, Martin M, Gunter L, and Patrick DL. Methods to determine the minimum important difference for a sexual event diary used by postmenopausal women with hypoactive sexual desire disorder.     

Effects of distraction using virtual reality glasses during lumbar punctures in adolescents with cancer

PURPOSE/OBJECTIVES: To determine the effects of virtual reality (VR) glasses on adolescents with cancer undergoing lumbar punctures (LPs). DESIGN: Pilot study using an experimental, control group design. SETTING: In-hospital oncology clinic. SAMPLE: 30 adolescents with cancer (17 in the VR and 13 in the control group) undergoing frequent LPs. METHODS: Subjects were randomly assigned to groups. Both groups received standard intervention during the LP, but the experimental group also wore VR glasses and watched a video. Following the LP, both groups rated their pain using a visual analog scale (VAS) and were interviewed to evaluate their experience. MAIN RESEARCH VARIABLES: Pain, subjective evaluation of experience. FINDINGS: Although VAS pain scores were not statistically different between the two groups (p = 0.77), VAS scores tended to be lower in the VR group (median VAS of 7.0, range 0-48) than in the control group (median VAS of 9.0, range 0-59). 77% of subjects in the experimental group said the VR glasses helped to distract them from the LP. CONCLUSIONS: VR glasses are a feasible, age-appropriate, nonpharmacologic adjunct to conventional care in managing the pain associated with LPs in adolescents. IMPLICATIONS FOR PRACTICE: The clinical application of various age-appropriate distracters to reduce pain in adolescents undergoing painful procedures should be explored.     

Challenging Behaviours in Dementia: a Project at Hornsby/Ku-Ring-Gai Hospital

Abstract: This paper introduces a two year study at Hornsby/Ku-Ring-Gai Hospital which aims to shed more light on the nature of behaviour problems in dementia, and on methods of dealing with them. Rather than trialing a standard therapeutic technique across a range of behaviours, the project attempts to reflect what is often a complex clinical situation not amenable to standard answers. A series of interventions is being instituted in a controlled trial on the assumption that each case is idiosyncratic both in aetiology and other variables which affect treatment choice. Data are collected on quantitative and qualitative aspects of each case, including presumed causes of the behaviour. Outcome is assessed two and five months after the intervention using measures of patient behaviour, and of carer distress, coping and perception of the problem.     

Involvement of multiple developmental genes on chromosome 1p in lung tumorigenesis

Lung cancer is the leading cause of cancer death in North America. Despite advances in lung cancer treatment, the overall 5 year survival rate for those diagnosed with the disease is bleak presumably due to the late stage of diagnosis. Owing to the difficulty of early detection, preneoplastic specimens are rare. However, studying both preinvasive and invasive stages of disease is necessary to fully understand lung cancer progression. Aberration of chromosome arm 1p is common in lung and other cancers. In this study, we used a genomic array with complete tiling coverage of 1p to profile preinvasive and invasive squamous non-small cell lung carcinoma samples. With this technology, multiple novel submegabase alterations were identified. Three of the 1p alterations harbored genes belonging to gene families known to be involved in cancer development through either the Wnt or the Notch developmental pathways. Our finding of a 0.4 Mb amplified region at 1p36.12 containing WNT4 in preinvasive lung cancer, coupled with the identification of three additional alterations in invasive tumors that also contain genes related to the Notch and Wnt pathways, strongly suggests an intricate role of these pathways in early and late stages of lung cancer development. Furthermore, ectopic expression of DVL1, LRP8 and Notch2 in malignant lung tissue validates the biological impact of these genetic alterations. Importantly, this implication of pathways known only to be activated in fetal lung development lends support to the proposed model of lung cancer ontology whereby tumors arise from dysregulated pleuripotent stem cells.     

Annual review of patients with sleep apnea/hypopnea syndrome--a pragmatic randomised trial of nurse home visit versus consultant clinic review

BACKGROUND: This pragmatic randomised, controlled trial investigated annual review of patients with sleep apnea/hypopnea syndrome (SAHS). Clinical outcomes and costs were compared for consultant clinic review versus specialist nurse home visit. METHOD: One hundred and seventy-four patients were randomised to annual review by consultant clinic appointment or by specialist nurse home visit. SAHS symptoms, Epworth score, hospital anxiety and depression scale (HADS), Short Form-36 (SF-36) and hours of use of constant positive airway pressure (CPAP) were measured before and 3 months after review. The costs and patient preference for review were determined. RESULTS: After review, both groups significantly increased CPAP use (mean (SD) increase: nurse, 0.66 (1.71) h; consultant, 0.45 (1.69) h) and reduced symptom scores (nurse, -2 (7); consultant, -3 (9)), compared to baseline. There were no differences between groups in these improvements, or in HADS or SF-36 scores. Average duration of a nurse home visit, excluding travel time, was 26 (6) min. Total NHS cost per visit was 52.26 UK pounds (49.85) ($83.62 (79.76)), of which 6.57 UK pounds (1.43) ($10.51 (2.29)) reflected time spent with the patient and the remainder was travel cost. Average duration of consultant review was 10 (6) min, total NHS cost 6.21 UK pounds (3.99) ($9.94 (6.38)). However, the cost to the patient of attending the clinic was 23.63 UK pounds (23.21) ($37.81 (37.13)). Patient preference for review was nurse 16%, consultant 19%, and no preference 65%. CONCLUSION: Following annual review, use of CPAP increased and symptoms improved. Outcomes were similar for consultant and nurse led review. Home visits were expensive for the healthcare provider, whereas clinic attendance incurred substantial costs to the patient. The majority of patients would accept nurse review for their sleep apnea management.     

OCGR array: an oral cancer genomic regional array for comparative genomic hybridization analysis

Genetic alterations have been recognized as important events in the carcinogenesis of oral squamous cell carcinoma (OSCC) and have been used as predictors of progression risk. In this study, we have designed an oral cancer-specific human bacterial artificial chromosome (BAC) array, called the oral cancer genomic regional array (OCGR), to detect and fine map copy number alterations in OSCC. This array contains a total of approximately 45 Mbp coverage of nine chromosomal regions reported to be involved in the progression of oral cancer. We demonstrate the detection of copy number alterations in 14 microdissected clinical specimens in each of the nine regions. These include both copy number increases and decreases. Although the number of regions selected for this first generation array is small, we observed multiple segmental changes. In some cases, we observed single BAC clone alterations at 7p11 and 11q13 which contain EGFR and cyclin D1 respectively highlighting the need for high resolution detection techniques. Array comparative genomic hybridization (CGH) complements traditional methods for detecting genetic alterations in OSCC (such as microsatellite and CGH analysis) by improving the detection of segmental copy number alterations to single BAC clone resolution. This work represents the first attempt at the construction of an oral cancer-specific CGH array.     

The role of cardiac morbidity in short- and long-term mortality in injured older patients who survive initial resuscitation

BACKGROUND: Elderly patients are an increasingly larger group of injured trauma care patients. Comorbidities influence outcome. Little is known of short- and long-term mortality in the elderly who survive initial resuscitation. METHODS: Short- and long-term mortality was retrospectively analyzed in 363 consecutively injured patients (Injury severity score >15) surviving more than 3 days after admission to a level 1 trauma center (including 197 patients >60 years). Cardiac morbidity was the focus. RESULTS: Survival to hospital discharge was similar comparing older patients with the entire group. Mortality increased incrementally with age. In older patients, cardiac morbidity was observed in 28% (fatal in 7); 2-year mortality was 36% (older group) and 60% (patients sustaining cardiac complications). Most elderly (80%) were discharged to long-term care. CONCLUSIONS: Elderly who survive initial resuscitation are as likely to survive to discharge as younger patients, but long-term survival is significantly lower as age increases. Cardiac morbidity is associated with higher long-term mortality. Most elderly are discharged to long-term care.     

The role of aromatase inhibitors in early breast cancer

Opinion statement The role of hormonal therapy for the treatment of patients with early stage breast cancer has been evaluated in many studies. The results of these studies establish tamoxifen as the gold standard of hormonal therapy for the adjuvant treatment of hormone receptorpositive invasive breast cancer in pre- and postmenopausal women. Studies show tamoxifen reduces the risk of invasive breast cancer in women at increased risk for the disease, including women with ductal carcinoma in situ. Tamoxifen has adverse effects such as hot flashes, increased risk of uterine cancer in postmenopausal women, and rare occurrence of thromboembolic disease. Despite the multiple therapeutic roles of tamoxifen, alternatives are needed. Aromatase inhibitors (AI) are drugs with antiestrogenic activity. AIs function by inhibiting the peripheral conversion of adrenally synthesized androstenedione to estradiol through inhibition of the aromatase enzyme. AIs do not suppress estradiol synthesis by the ovary adequately. Therefore, AIs are effective in reducing circulating estradiol levels in postmenopausal women, but not premenopausal women. Selective nonsteroidal AIs, including anastrozole (Arimidex; AstraZeneca, Wilmington, DE) and letrozole (Femara; Novartis, East Hanover, NJ), and the steroidal AI exemestane (Aromasin; Pharmacia, Peapack, NJ) have been associated with increased specificity and improved therapeutic index compared to nonselective AIs such as aminoglutethamide. Nonsteroidal and steroidal AIs have demonstrated to be superior to megestrol acetate in second-line therapy of postmenopausal women with metastatic breast cancer, and selective nonsteroidal AIs have shown to be superior to tamoxifen in first-line therapy of postmenopausal women with metastatic breast cancer. The ATAC (Arimidex, tamoxifen, alone, or in combination) trial is the only published randomized trial comparing the efficacy of an AI to tamoxifen for the adjuvant treatment of women with early breast cancer. This large study showed that at a median follow-up time of 33 months, anastrozole alone results in significant improvement in disease-free survival rates, reduction in contralateral breast cancers, and increased tolerability, compared to tamoxifen in postmenopausal women. Although the long-term effects of AIs are not known, the early positive results of the ATAC trial led to the approval of anastrozole by the US Food and Drug Administration for use as adjuvant hormonal therapy for postmenopausal women with hormone receptor-positive invasive breast cancer. Thus, there is an alternative to tamoxifen for postmenopausal women with relative/absolute contraindications to tamoxifen use or patients who choose not to take tamoxifen because of its side-effect profile. New AIs may challenge the position of tamoxifen as the gold standard for the treatment of early stage breast cancer in postmenopausal women.     

A neonatal swine model for peanut allergy.

BACKGROUND: Peanut allergy represents a significant health threat in the United States. The factors contributing to the severity of the allergic response and the immunopathogenic mechanisms underlying peanut allergy remain to be completely characterized. As yet, no animal model has been developed that will completely mimic the physical, immunologic, and histologic features of food allergy. OBJECTIVE: The purpose of this investigation was to develop a neonatal pig model of peanut allergy that would mimic the allergic symptoms and the immunologic and histologic profile of human peanut allergy. METHODS: Newborn piglets sensitized intraperitoneally with peanut extract and cholera toxin were orally challenged repeatedly with peanut meal. Physical symptoms, including emesis, lethargy, diarrhea, and respiratory distress, were monitored to determine the allergic response. Immunologic assessment was conducted through use of skin testing and the antigenic response to peanut proteins. Histologically, tissues derived from the esophagus, stomach, small intestine, and colon were assessed for morphologic changes after the oral challenge. RESULTS: Peanut-sensitized pigs responded with physical symptoms that mimicked those seen in double-blinded, placebo-controlled oral food challenges to peanuts in children and adults. Skin testing suggested an IgE-mediated response; this was confirmed by a negative passive cutaneous anaphylaxis response of heat-treated sera obtained from peanut-sensitized animals. Damage to villi of the small intestine was similar to that seen in endoscopically obtained tissue specimens from certain food-allergic individuals. CONCLUSION: The neonatal pig model of peanut allergy mimics the physical and immunologic characteristics of peanut allergy in human beings. The model will be useful for determining IgE-mediated mechanisms and conducting endoscopic histologic assessment of tissues and immunotherapeutic intervention strategies with repeated allergen challenges.