To conduct a systematic review to determine clearance rates and adverse effects of topical imiquimod or fluorouracil therapy in the treatment of nonmelanoma skin cancers such as basal (BCC) and ...squamous cell carcinoma (SCC), and to develop recommendations for the use of topical imiquimod or fluorouracil to treat BCC and SCC.
MEDLINE, CANCERLIT, and Cochrane databases.
Prospective, retrospective, and case studies in English containing a minimum of 4 subjects and a 6-month follow-up or posttreatment histologic evaluation.
We calculated the rate of clearance and adverse effects for BCC subtypes and invasive and in situ SCC treated with topical imiquimod or fluorouracil.
Clearance rates varied by drug regimen, and most of the studies lacked long-term follow-up. Imiquimod use produced the following clearance rates: 43% to 100% for superficial BCC, 42% to 100% for nodular BCC, 56% to 63% for infiltrative BCC, 73% to 88% for SCC in situ, and 71% for invasive SCC. Fluorouracil use produced the following clearance rates: 90% for superficial BCC and 27% to 85% for SCC in situ. Up to 100% and 97% of patients applying imiquimod and fluorouracil, respectively, experienced at least 1 adverse event. Adverse event intensity ranged from mild to severe; erythema, pruritus, and pain were common.
Evidence supports the use of topical imiquimod as monotherapy for superficial BCC and topical fluorouracil as monotherapy for superficial BCC and SCC in situ. Based on the available evidence, the strength of any recommendations for the use of these 2 agents in the primary treatment of these tumors is weak. We recommend that their use be limited to patients with small tumors in low-risk locations who will not or cannot undergo treatment with better-established therapies for which long-term clearance rates have been determined. Long-term clinical follow-up is essential for patients treated with topical imiquimod or fluorouracil. Limitations of therapy include high rates of adverse effects, lower clearance rates than other treatment modalities, dependence on patient adherence to treatment, and higher costs than other therapies.
Sickle cell disease (SCD) is an inherited disease characterized by hemolysis, anemia, and vaso-occlusion leading to substantial morbidity and mortality. Development of prior pharmacologic therapies ...exclusively utilized vaso-occlusive crisis (VOC) as a clinical efficacy endpoint; however, this focus on VOC did not capture the full extent of disease symptomatology and complications and slowed the development of new therapies. Voxelotor, a hemoglobin S polymerization inhibitor, was recently approved in the United States for the treatment of SCD in adults and adolescents 12 years of age and older through an accelerated approval pathway. The rapid approval and availability of voxelotor was facilitated in a collaborative effort with the US Food and Drug Administration (FDA), using hemoglobin, a biologic surrogate endpoint, as reasonably likely to predict clinical benefit. Use of this new endpoint was supported by FDA-led multistakeholder discussions with physician and patient communities to identify unmet needs and potential clinical trial endpoints, as well as by a company-sponsored analysis of external patient-level data to demonstrate a correlation between hemoglobin change and stroke risk. A two-part phase 3 study was used to allow for rank ordering of key secondary endpoints based on a planned interim analysis. Continued open communication with the FDA was essential to gain agreement on hemoglobin as a novel endpoint and to address the unmet and urgent need of new therapies for SCD.
STREET A.F., COUPER J.W., LOVE A.W., BLOCH S., KISSANE D.W. & STREET B.C. (2010) European Journal of Cancer Care19, 234–242 Psychosocial adaptation in female partners of men with prostate cancer
The ...objective was to explore the psychosocial adaptation of female partners living with men with a diagnosis of either localized or metastatic prostate cancer. Semi‐structured qualitative interviews were conducted with 50 women at two time points (baseline and 6 months later). The interviews examined emotions, experiences, attitudes to sexual and continence issues and treatment decision making. As part of a larger prospective observational study, demographic data and scores for depression and anxiety were collected. Initial analysis demonstrated that the group of 11 women assessed as distressed on the anxiety and depression measures described reduced coping skills and poorer adaptation after 6 months. In contrast, the 39 women in the non‐distressed group reported emotional adaptation that fitted the Lazarus and Folkman pattern of coping through appraisal of the impact of the diagnosis on their partner and themselves, appraisal of coping strategies and reappraisal of the situation. A surprise finding was the high level of resilience displayed by majority of these women. Results suggest that a psychosocial intervention could strengthen healthy adaptation and provide better coping skills for distressed couples.
Background: A congenital form of idiopathic intestinal bile acid malabsorption (IBAM) has been associated with dysfunctional mutations in the ileal apical sodium-dependent bile acid transporter ...(ASBT). The aim of this study was to determine whether mutations in the ASBT gene (SLC10A2) predispose to the development of adult-onset idiopathic bile acid malabsorption and chronic watery diarrhea. Methods: Genomic DNA was obtained from 13 adult IBAM patients previously diagnosed on the basis of clinical data, response to cholestyramine, and abnormal 75Se-homocholic acid taurine (SeHCAT) test values. The ASBT gene was screened for the presence of mutations or polymorphisms by single-stranded conformation polymorphism analysis (SSCP) and DNA sequencing. Results: ASBT gene polymorphisms were detected in 5 of the 13 adult IBAM patients. Four patients were heterozygous for a common polymorphism in exon 3, leading to an alanine to serine substitution at codon 171 (A171S). An additional subject was heterozygous for a polymorphism in exon 1 that causes a valine to isoleucine substitution at codon 98 (V98I). These functional polymorphisms were also found in unaffected subjects and do not appear to affect ASBT function. Conclusions: Adult-onset IBAM is not directly related to dysfunctional mutations in the coding region or intron/exon junctions of the SLC10A2 gene. In the absence of apparent ileal disease or intestinal motility defects, inappropriate down-regulation of the ileal bile acid transporter or defects in ileocyte transfer of bile acids into the portal circulation could explain this form of adult IBAM.
Atopic dermatitis (AD) patients have sensitive skin with impaired barrier function. Lyocell is a cellulosic fiber that offers unique characteristics and may be suitable for use by AD patients.
To ...compare preferences of subjects with atopic dermatitis and normal skin for 100% lyocell clothing and bedding versus 100% cotton fabrics.
Thirty subjects were enrolled and randomly selected to use cotton or lyocell shirts, pajamas, and bedding for 1 week. Following a 1-week washout period, participants wore the other fabric for 1 week. At the end of each week, participants completed a preference questionnaire, and AD subjects also rated daily itching on a visual analog scale. A random subset of AD and normal participants underwent measurement of transepidermal water loss (TEWL).
Overall, there was a significant preference for lyocell (vs cotton) for its softness, temperature control, moisture control, and wrinkle resistance. AD subjects did not have stronger fabric preferences than did normal subjects. Although not significant, lower average itching and decreased TEWL were seen in participants while they wore lyocell.
Lyocell is superior to cotton in many performance characteristics and equivalent to cotton for itch reduction. Lyocell is currently available as a beneficial fabric to improve patient comfort.
Grief occurs with loss of symbolically important connections and involves intense emotional reactions and changes to our experiences of self, the world, and the future.Individual responses reflect ...factors such as personality and life history, social context and cultural practices, and the symbolic magnitude of the loss. Grieving can be a relatively slow and uneven process, so applying prescriptive stages or goals to individuals' experiences can be unhelpful. Although most people are resilient in the face of loss and do not require special interventions, health professionals can contribute by empathic use of communication skills to facilitate the grieving process. A minority will struggle with their grief and experience prolonged, intense, or problematic reactions. Psychiatric comorbidities including depression and anxiety disorders can occur, and a distinct diagnosis of complicated grief disorder has been proposed. Health professionals can identify complicated grief reactions and ensure patients receive specialised treatment, including intensive grief therapy and medication where indicated. Assessment methods are summarised to assist health professionals in providing a continuum of care for those who are grieving.
TNK-tissue plasminogen activator (TNK-TPA) is a genetically engineered variant of TPA, which in experimental models has a slower plasma clearance and greater fibrin specificity and is 80-fold more ...resistant to plasminogen activator inhibitor-1 than alteplase TPA.
The thrombolysis in Myocardial Infarction (TIMI) 10A trial was a Phase 1, dose-ranging pilot trial designed to evaluate the pharmacokinetics, safety, and efficacy of TNK-TPA in patients with acute myocardial infarction. One hundred thirteen patients with acute ST-segment elevation myocardial infarction presenting within 12 hours and without contraindications to thrombolysis were enrolled and treated with a single bolus of TNK-TPA over 5 to 10 seconds with doses ranging from 5 to 50 mg. TNK-TPA demonstrated a plasma clearance of 151 +/- 55 mL/min and a half-life of 17 +/- 7 minutes. Comparable values for wild-type TPA are 572 +/- 132 mL/min and 3.5 +/- 1.4 minutes, respectively. Systemic fibrinogen and plasminogen levels fell by only 3% and 13%, respectively, at 1 hour after TNK-TPA administration. TIMI grade 3 flow at 90 minutes was achieved in 57% to 64% of patients at the 30- to 50-mg doses. Seven patients (6.2%) experienced a major hemorrhage, which occurred at a vascular access site in six patients.
TNK-TPA has a prolonged half-life so it can be administered as a single bolus. TNK-TPA appears to be very fibrin specific, and the initial patency and safety profiles are encouraging. Further study of this new thrombolytic agent is ongoing.
Largemouth Bass (Micropterus salmoides) is a common predator and popular sport fish in tidal freshwater streams and lakes of North America. Tidal freshwater streams of Chesapeake Bay watershed, the ...largest estuary of the United States, differ remarkably in availability of submerged aquatic vegetation (SAV) and suitability for spawning habitat for M. salmoides. After scoring nursery habitat attributes of size and habitat quality, I combined scores to form indices for 141 nursery habitats of the Chesapeake Bay watershed. Average index for nursery habitat quality was positively related to the relative abundance of juvenile M. salmoides. For two important coastal fisheries for M. salmoides, over half of highly indexed nursery habitats were expected to be negatively impacted by projected sea level rise (SLR). Innovative strategies aimed at conserving populations of M. salmoides may include identifying habitats vulnerable to such long-term habitat changes and either protecting important habitats or managing future expectations for these populations.
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