Impact of peer support on inpatient and outpatient payments among people with Type 2 diabetes: a prospective cohort study.

AIM: To investigate the impact of a low-cost diabetes peer-support intervention, aimed at reducing inpatient and outpatient care utilization and healthcare payments, by conducting a cohort study that followed up a randomized controlled trial. METHODS: A total of 1121 adults with Type 2 diabetes were recruited through general practices in Cambridgeshire and Hertfordshire, UK, and were followed up for 3.25 financial years after 8-12 months of one-to-one, group or combined diabetes peer support and usual care. Use of, and payments for inpatient and outpatient services were fully recorded in the follow-up. Adjusted mean inpatient and outpatient payments per person were estimated using a two-part model after adjusting for baseline characteristics. RESULTS: The mean age of the recruited adults was 65.6±11.4 years, 60.4% were male, and 16.8% were insulin-treated. Compared with the control group, less healthcare utilization (especially non-elective inpatient care and outpatient consultations) was observed in each of the intervention groups, particularly the combined intervention group. Over the course of 3.25 financial years, significant reductions of 41% (£909.20 per head) were observed for overall inpatient payments (P<0.0001), 51% (£514.67 per head) for non-elective inpatient payments (P=0.005) in the combined intervention group, and 34% (£413.30 per head) and 32% (£388.99 per head) for elective inpatient payments in the one-to-one (P=0.029) and combined intervention (P=0.048) groups, respectively. CONCLUSIONS: Type 2 diabetes peer support, whether delivered using a one-to-one, group or combined approach was associated with reduced inpatient care utilization (particularly non-elective admissions) and payments over 3.25 years.

Kelp detritus: Unutilized productivity or an unacknowledged trophic resource?

Kelp beds are one of the most productive marine systems and, while little of this production is directly consumed, there is growing evidence that kelp detritus is an essential food source for many detrital and suspension feeders, and forms an important component of offshore sedimentary carbon pools. However, the extent of the contribution of kelp detritus to the nutrition of coastal fauna is not well resolved. In this study, we compare the contribution of phytoplankton, kelp detritus, and waste from fish cages to the diet of a sentinel suspension feeder, the blue mussel (Mytilus edulis) using stable isotopes. We found a significant depletion in both 13C and 15N in kelp tissue with age (distance from stipe to the deteriorating distal end of the kelp frond) which may have biased dietary estimates in previous studies which have applied isotopic source values derived from fresh kelp. Our mixing models indicate that macroalgal detritus formed 59% of the diet of the mussels in Berehaven, Bantry Bay, Ireland. We support the isotopic mixing model results by modelling the relative production of phytoplankton, kelp, and salmon farm waste, and found the supply of C and N from kelp and phytoplankton far exceeded the requirements of the mussels with much less coming from the nearby fish cages. Monthly chlorophyll measurements indicated there was only sufficient phytoplankton density to support mussel growth during the spring and autumn, explaining our observation of patterns in the relative importance of utilization of kelp detritus. Where there is pressure to harvest kelp beds, this study highlights the supporting ecosystem service they provide as an important dietary source in coastal food webs and emphasises the need for appropriate management measures for this resource.

Candida Endocarditis: A Review of the Pathogenesis, Morphology, Risk Factors, and Management of an Emerging and Serious Condition.

Infective endocarditis is a significant healthcare burden due to the associated high mortality and complications. Endocarditis caused by both Candida albicans (C. albicans) and non-Candida albicans Candida (NCAC) species has been associated with a substantial rise in in-hospital morbidity and mortality. We used the Pubmed database to identify 47 out of 101 articles that had met our inclusion and exclusion criteria. We had put in place a broad inclusion criterion with no age or gender restrictions. These 47 articles included abstracts, 11 review articles, 13 case reports, 10 research articles, 1 clinical trial report, 1 meta-analysis, and other research articles. And they comprehensively cover the pathogenesis, risk factors, and management of infections caused by C. albicans and NCAC species in the past 26 years. The articles we scanned provided us with information on different associations in correlation to multiple types of Candida species. Here, we discuss the association between Candida and endocarditis, a major cause of morbidity and mortality in both C. albicans and NCAC. We also present our understanding regarding this interesting association and attempt to address some of the recurring questions.

Longitudinal studies of effects of divorce on children in Great Britain and the United States.

National, longitudinal surveys from Great Britain and the United States were used to investigate the effects of divorce on children. In both studies, a subsample of children who were in two-parent families during the initial interview (at age 7 in the British data and at ages 7 to 11 in the U.S. data) were followed through the next interview (at age 11 and ages 11 to 16, respectively). At both time points in the British data, parents and teachers independently rated the children's behavior problems, and the children were given reading and mathematics achievement tests. At both time points in the U.S. data, parents rated the children's behavior problems. Children whose parents divorced or separated between the two time points were compared to children whose families remained intact. For boys, the apparent effect of separation or divorce on behavior problems and achievement at the later time point was sharply reduced by considering behavior problems, achievement levels, and family difficulties that were present at the earlier time point, before any of the families had broken up. For girls, the reduction in the apparent effect of divorce occurred to a lesser but still noticeable extent once preexisting conditions were considered.

Association Between Cerebrovascular Accident and Vasculitis: Myth or Reality?

This article aims to determine an association between vasculitis and cerebrovascular accidents (CVA) and the ideal management plan to decrease the chances of CVA in vasculitis patients. We also attempt to find a preferred treatment regimen that decreases the complications of CVAs in vasculitis patients, thereby resulting in reduced mortality and morbidity. We reviewed both free-access full-text articles and the abstracts of articles behind a paywall. We used the PubMed database and reviewed 89 articles that matched our inclusion and exclusion criteria. In all, 42 out of the 89 articles had the most relevant data for our article. We used the following keywords to search the database: vasculitis, stroke, cerebrovascular accident, ischemic, arteritis, and steroid. We found an association between subtypes of vasculitis, mostly large vessel vasculitis and CVA. We could not identify a specific cutoff value for specific inflammatory markers that can increase the risk of developing CVA. Besides, there are no formal guidelines for the dosage or the route of administration for corticosteroids, which are the cornerstone of treatment for most vasculitis. We found that male giant cell arteritis (GCA) patients have a higher chance of developing CVA than females, Also interestingly, anemia was found to be protective against CVA development in GCA patients. Sometimes, CVA can happen due to the effects of treatments of some types of vasculitis. We recommend establishing further studies about other subtypes of vasculitis and their associations with stroke.

Mitigation assessment of vegetated drainage ditches for collecting irrigation runoff in California.

Widespread contamination of California water bodies by the organophosphate insecticides diazinon and chlorpyrifos is well documented. While their usage has decreased over the last few years, a concomitant increase in pyrethroid usage (e.g., permethrin) (replacement insecticides) has occurred. Vegetated agricultural drainage ditches (VADD) have been proposed as a potential economical and environmentally efficient management practice to mitigate the effects of pesticides in irrigation and storm runoff. Three ditches were constructed in Yolo County, California for a field trial. A U-shaped vegetated ditch, a V-shaped vegetated ditch, and a V-shaped unvegetated ditch were each amended for 8 h with a mixture of diazinon, permethrin, and suspended sediment simulating an irrigation runoff event. Water, sediment, and plant samples were collected spatially and temporally and analyzed for diazinon and permethrin concentrations. Pesticide half-lives were similar between ditches and pesticides, ranging from 2.4 to 6.4 h. Differences in half-distances (distance required to reduce initial pesticide concentration by 50%) among pesticides and ditches were present, indicating importance of vegetation in mitigation. Cis-permethrin half-distances in V ditches ranged from 22 m (V-vegetated) to 50 m (V-unvegetated). Half-distances for trans-permethrin were similar, ranging from 21 m (V-vegetated) to 55 m (V-unvegetated). Diazinon half-distances demonstrated the greatest differences (55 m for V-vegetated and 158 m for V-unvegetated). Such economical and environmentally successful management practices will offer farmers, ranchers, and landowners a viable alternative to more conventional (and sometimes expensive) practices.

Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination.

Three distinct DNA ligases, I to III, have been found previously in mammalian cells, but a cloned cDNA has been identified only for DNA ligase I, an essential enzyme active in DNA replication. A short peptide sequence conserved close to the C terminus of all known eukaryotic DNA ligases was used to search for additional homologous sequences in human cDNA libraries. Two different incomplete cDNA clones that showed partial homology to the conserved peptide were identified. Full-length cDNAs were obtained and expressed by in vitro transcription and translation. The 103-kDa product of one cDNA clone formed a characteristic complex with the XRCC1 DNA repair protein and was identical with the previously described DNA ligase III. DNA ligase III appears closely related to the smaller DNA ligase II. The 96-kDa in vitro translation product of the second cDNA clone was also shown to be an ATP-dependent DNA ligase. A fourth DNA ligase (DNA ligase IV) has been purified from human cells and shown to be identical to the 96-kDa DNA ligase by unique agreement between mass spectrometry data on tryptic peptides from the purified enzyme and the predicted open reading frame of the cloned cDNA. The amino acid sequences of DNA ligases III and IV share a related active-site motif and several short regions of homology with DNA ligase I, other DNA ligases, and RNA capping enzymes. DNA ligases III and IV are encoded by distinct genes located on human chromosomes 17q11.2-12 and 13q33-34, respectively.

SMi'S 4th Annual Orphan Drugs and Rare Diseases Conference (October 19-20, 2015--London, UK).

The story of rare diseases is a story of people. Often very young, and usually with little hope of treatment, it is often a desperately sad and tragic story, but increasingly a story of hope. Statistics are inescapable when discussing the subject: small numbers of patients in huge populations, the massively disproportionate contribution to pediatric mortality, and the necessarily high prices for rare drugs. Almost every speaker at the SMi's Fourth Orphan Drugs and Rare Diseases conference provided figures that illustrated just how different this area is to the macro-world of the blockbuster drug.

Epidermal cytoplasmic antigens: II. Concurrent presence of antigens of different specificities in normal human skin.

Cytoplasmic antigens of 3 different specificities are expressed concurrently in the epidermis of normal human skin. They differ by their location in distinct layers of the epidermis. One type is present in all epidermal cells, another only in cells of the superficial layers, and the third only in basal cells. All 3 antigens were present in 10 specimens of normal human skin. The superficial and basal cell antigens were absent in 4 basal cell epitheliomas and 3 squamous cell carcinomas. This finding, together with the stratification of the antigens in different layers of the skin, suggests epidermal cytoplasmic antigens are differentiation antigens.

Biodistribution and radiation dosimetry of stabilized 99mTc-exametazine-labeled leukocytes in normal subjects.

UNLABELLED: Labeling leukocytes with 99mTc-exametazime is a validated technique for imaging infection and inflammation. A new radiolabeling technique has recently been described that enables leukocyte labeling with a more stable form of 99mTc-exametazime. A normal value study of stabilized 99mTc-exametazime-labeled leukocytes has been performed, including biodistribution and dosimetry estimates in normal subjects. METHODS: Ten volunteers were injected with stabilized 99mTc-exametazime-labeled autologous leukocytes to study labeled leukocyte kinetics and dosimetry in normal subjects. Serial whole-body imaging and blood sampling were performed up to 24 h after injection. Cell-labeling efficiency and in vivo viability, organ dosimetry, and clearance calculations were obtained from the blood samples and imaging data as well as urine and stool collection up to 36 h after injection. RESULTS: Cell-labeling efficiency of 87.5% +/- 5.1% was achieved, which is similar to or better than that reported with the standard preparation of 99mTc-exametazime. In vivo stability of the radiolabeled leukocytes was also similar to in vitro results with stabilized 99mTc-exametazime and better than previously reported in vivo stability for nonstabilized 99mTc-exametazime-labeled leukocytes. Organ dosimetry and radiation absorbed doses were similar with a whole-body absorbed dose of 1.3 x 10(-3) mGy/ MBq. Urinary and fecal excretion of activity was minimal, and visual assessment of the images showed little renal parenchymal activity and no bowel activity up to 2 h after injection. CONCLUSION: Cell labeling and in vivo stability appear improved compared with the leukocytes labeled with the nonstabilized preparation of 99mTc-exametazime. There are advantages in more cost-effective preparation of the stabilized 99mTc-exametazime and an extended window for clinical usage, with good visualization of abdominal structures on early images. No significant increase in specific organ and whole-body dosimetry estimates was noted compared with previous estimates using nonstabilized 99mTc-exametazime-labeled leukocytes.

Infrastructure for reaching disadvantaged consumers: telecommunications in rural and remote nursing in Australia.

Both consumers and health service providers need access to up-to-date information, including patient and practice guidelines, that allows them to make decisions in partnership about individual and public health in line with the primary health care model of health service delivery. Only then is it possible for patient preferences to be considered while the health of the general population is improved. The Commonwealth Government of Australia has allocated $250 million over five years, starting July 1, 1997, to support activities and projects designed to meet a range of telecommunication needs in regional, rural, and remote Australia. This paper defines rural and remote communities, then reviews rural and remote health services, information, and telecommunication technology infrastructures and their use in Australia to establish the current state of access to information tools by rural and remote communities and rural health workers in Australia today. It is argued that a suitable telecommunication infrastructure is needed to reach disadvantaged persons in extremely remote areas and that intersectoral support is essential to build this infrastructure. In addition, education will make its utilization possible.

Analysis of persistent disease on the ear following Mohs surgery.

A retrospective study of 338 patients with malignant lesions of the auricle is presented. The results of treatment using Mohs microscopically controlled surgery and conventional surgical excision are compared and the high incidence of recurrence is stressed. The incidence, etiology, pathology, and subclinical extension of auricular tumors are discussed. The treatment of choice is Mohs microscopically controlled surgery and a plea is made for a more radical therapeutic approach to these often casually treated neoplasms.

Risk factors for local recurrence of primary cutaneous squamous cell carcinomas. Treatment by microscopically controlled excision.

Four hundred fourteen primary cutaneous squamous cell carcinomas were treated by microscopically controlled excision. A five-year mortality-table adjusted cure rate of 93.3% was achieved. The following six parameters were analyzed for correlation with the local recurrence rate: sex, age, lesion diameter, history of previous therapy, anatomic site, and number of stages of Mohs' surgery required for treatment. Only the number of stages correlated significantly with the recurrence rate. However, subpopulations at high risk for recurrent disease could be identified. These consisted of male patients younger than 60 years of age, male patients requiring five or more stages of Mohs' surgery, and patients of either sex with carcinoma of the lower extremity. Modifications of microscopically controlled excision may be warranted in selected patients.

P53 oncoprotein expression and gene mutations in some keratoacanthomas.

OBJECTIVE: To analyze the relationship of p53 oncoprotein overexpression in most keratoacanthomas (KAs) with gene mutations. DESIGN: Expression of p53 oncoprotein in immunohistochemical staining and its correlation to gene mutations in DNA extracted from KAs and tested in single-strand conformational polymorphism (SSCP) analysis and direct sequencing. SETTING: A micrographic surgery unit and a dermatopathology unit at a university medical center. PATIENTS: Sixteen formalin-fixed, paraffin-embedded skin biopsy specimens were retrieved from dermatopathology archives. Biopsies were performed to establish the diagnosis of KA before surgical treatment. MAIN OUTCOME MEASURES: Intensity of staining in immunohistochemical testing for p53 oncoprotein expression and sequencing of gene mutations. RESULTS: Immunohistochemical staining of 16 KA specimens detected p53 oncoprotein in 15 (94%), distributed as strong in 4 (25%), moderate in 2 (12%) mild in 9 (56%), and negative in 1 (6%), compared with control specimens. Specimens were screened by SSCP for mutations in the p53 gene, and 1 specimen showed a potential mutation in exon 7. Direct sequencing of the samples revealed 2 point mutations. One specimen showed a change of G:A for A:G in codon 146 of exon 5, predicting an amino acid substitution of tryptophan for a stop codon. Another specimen revealed a change of T:A for A:T in codon 234 of exon 7, predicting an amino acid substitution of tyrosine for asparagine. CONCLUSIONS: Ninety-four percent of KA specimens evaluated had detectable p53 oncoprotein. This protein was associated with a point mutation in the p53 gene in 2 of 16 KAs evaluated. In a small fraction of KAs, overexpression of p53 oncoprotein may be associated with point mutations in the p53 gene.

Radiotherapy of periocular basal cell carcinomas: recurrence rates and treatment with special attention to the medical canthus.

Basal cell carcinomas of the eyelids, especially those in the medial canthal area, may cause extensive local destruction. Recurrent tumours are more aggressive and become progressively more difficult to treat; this is especially true for postirradiated recurrent, medial canthal, basal cell carcinomas. Tumours in this area should thus be treated by a technique which allows tissue sampling in order to gauge the adequacy of the treatment, with the goal being complete extirpation of the tumour. Excision monitored by frozen section control or Mohs' surgery is our recommendation based on a retrospective analyses of 631 eyelid basal cell carcinomas, half of which were primary tumours and half recurrent.

Scoliosis in Marfan's syndrome. Its characteristics and results of treatment in thirty-five patients.

Of sixty-four patients with Marfan's syndrome, thirty-five had scoliosis, which in 44 per cent began in the infantile and juvenile age periods. The curve patterns were double major right thoracic-left lumbar in 48 per cent and single right thoracic in 33 per cent. At the start of treatment the curves were severe (average, 72 degrees) and quite structural (average bending correction, 36 per cent). Seventy-four per cent of the thirty-five patients had back pain. Inadequately treated and untreated curves usually progressed to severe and painful deformity. Milwaukee brace treatment was generally unsuccessful because of the severity and rigidity of the curves or the poor maintenance of correction obtained. Spine fusion combined with Harrington rod instrumentation (fourteen patients) gave an average correction of 41 per cent with an average loss of 7 degrees (average follow-up, 2.3 years). Operative treatment of scoliosis is indicated in most patients with Marfan's syndrome.

Use of in vivo and in vitro assays for the characterization of mammalian excision repair and isolation of repair proteins.

Elucidation of the molecular mechanism of mammalian nucleotide excision repair requires the availability of purified proteins, DNA substrates with defined lesions and suitable repair assays. Repair assays introduced in recent years vary from testing individual steps and successions of steps in vitro to systems that closely reflect the entire process in vivo. In the first part of this review, an in vivo microinjection system is discussed. The second part of the article reviews an in vitro system for study of repair synthesis promoted by cell extracts. Both systems can be utilized as assays during the purification of protein factors that complement repair-defective xeroderma pigmentosum cells. The effect of purified repair proteins from other organisms on mammalian repair is also considered.

Effect of exogenous DNA fragments on human cell extract-mediated DNA repair synthesis.

Extracts from HeLa cells were used to study the susceptibility of repair synthesis in UV-irradiated plasmid DNA to inhibition by exogenously added nucleic acid. Purified DNA restriction fragments have little inhibitory effect on repair synthesis. However, activated calf thymus DNA fragments, genomic DNA fragments in cell extracts, and sonicated plasmid DNA all inhibited repair synthesis. Degraded DNA fragments arising from E. coli during bacterial plasmid purification were found to be particularly inhibitory. tRNA is not a potent inhibitor of in vitro repair synthesis. In order to observe efficient DNA repair synthesis mediated by human cell extracts, it is essential to prepare highly purified closed circular plasmid DNA, and we describe a reliable method for doing so.

Protein farnesyltransferase and adenosine receptors.

Many exciting advances in the treatment of cancer were presented at the symposium entitled 'Protein prenylation' which was chaired by Professor Richard A Gibbs (Wayne State University, Detroit, MI, USA). Prenylation, or the covalent attachment of isoprenoid lipids, is now recognized as an important component in the post-translational localization and functionalization of many cellular proteins. The majority of prenylated proteins are modified by one of two specific enzymes: protein farnesyl-transferase (FTase) and geranylgerany-ltransferase type I (GGTase-I). The finding that farnesylation of oncogenic forms of Ras proteins is required for expression of their transforming activity has led to FTase becoming an important target for anticancer drug design.

Anticoagulation strategies.

A number of individual presentations at this meeting dealt with the burgeoning field of anticoagulation strategies, and the fourth day (Wednesday) provided one of the most interesting symposia of the meeting, entitled 'Anticoagulation Strategies: Thrombin and Factor Xa Inhibition'. Chair RR Wexler (DuPont Merck, PA, USA) pointed out that classical anticoagulants, such as warfarin, suffer from poor oral bioavailability, lack of selectivity and short plasma half-life. In addition, there are safety issues, for instance, an increased risk of bleeding, and a large peak-to-trough ratio. Hirudin is a recently-approved thrombin inhibitor, but is suitable for parenteral administration only. New therapies are needed and many advances in this field were presented in the ensuing sessions.