Impact of procedural multimedia instructions for pH BRAVO testing on patient comprehension: a prospective randomized study.

The positive impact on patient comprehension and improved procedural outcomes when multimedia is utilized to convey instructions preprocedurally has been previously shown for gastrointestinal procedures such as colonoscopy. However, in gastroesophageal reflux testing (GERD), we continue to utilize verbal and written instructions to establish this diagnosis when we use BRAVO pH testing. This is arguably a more complex procedure involving stopping medications, placement of a device, and maintaining an accurate diary for the duration of the testing. We hypothesize that by utilizing multimedia to relay complex textual information, patients will have improved comprehension of periprocedural instructions thereby improving data entry and satisfaction of expectations during the procedure. Prospective randomized study of 120 patients undergoing endoscopic placement of the BRAVO pH monitoring capsule for evaluation of GERD receive either written preoperative instructions (control) or written plus video instructions (video group). A composite comprehension score was calculated using procedure-specific parameters of data entry over the 48-hour monitoring period. Patient satisfaction was evaluated on the basis of a five-point Likert scale. Extent of patient satisfaction was defined by the fulfillment of patient expectations. Exclusion criteria included patients who did not have access to the video or did not complete follow-up. Seventy-eight patients completed all follow-up evaluations. The video group (n = 44) had a significantly higher mean comprehension score when compared to the control group (n = 34) (9.6 ± 1.4 vs. 7.4 ± 2.0, P = 0.01). Overall satisfaction with instructions was significantly higher in the intervention group (91% vs. 47%, p 0.01). We detected no significant difference in comprehension or satisfaction scores in subgroup analyses of the video group comparing patients <65 and ≥65 years of age and by education level. Compared to standard written instructions, video instructions improved patient comprehension based on data evaluation, and satisfaction. Therefore, clinicians should consider incorporation of multimedia instructions to enhance patient periprocedural expectations and understanding of reflux pH testing using the BRAVO procedure.

Ammonia oxidizer populations vary with nitrogen cycling across a tropical montane mean annual temperature gradient.

Functional gene approaches have been used to better understand the roles of microbes in driving forest soil nitrogen (N) cycling rates and bioavailability. Ammonia oxidation is a rate limiting step in nitrification, and is a key area for understanding environmental constraints on N availability in forests. We studied how increasing temperature affects the role of ammonia oxidizing archaea (AOA) and bacteria (AOB) in soil N cycling and availability by using a highly constrained natural mean annual temperature (MAT) elevation gradient in a tropical montane wet forest. We found that net nitrate (NO3- ) bioavailability is positively related to MAT (r2  = 0.79, P = 0.0033), and AOA DNA abundance is positively related to both NO3- availability (r2  = 0.34, P = 0.0071) and MAT (r2  = 0.34, P < 0.001). In contrast, AOB DNA was only detected in some soils across the gradient. We identified three distinct phylotypes within the AOA which differed from one another in abundance and relative gene expression. In addition, one AOA phylotype increased in abundance with MAT, while others did not. We conclude that MAT is the primary driver of ecosystem N availability across this gradient, and AOA population size and structure appear to mediate the relationship between the nitrification and N bioavailability. These findings hold important implications for nutrient limitation in forests and feedbacks to primary production under changing climate.

The Relationship Between Soil Arthropods and the Overwinter Survival of Ixodes scapularis (Acari: Ixodidae) Under Manipulated Snow Cover.

We explored the relationship between the diversity and abundance of the soil arthropod predator community and the overwinter survival of engorged larval Ixodes scapularis Say under variable snow cover in a hardwood forest. We reduced the snow cover over 30 soil core field microcosms, simulating predicted changes in snow pack in the northeastern United States. An additional 29 microcosms were used as references with no snow pack manipulation. Each microcosm contained 15 engorged larval I. scapularis. We expected lower soil temperature without insulating snow cover to reduce tick survival. However, we observed that reduced snow cover had no effect, with 44.2 and 44.7% overwintering successfully in the reference and snow-removal plots, respectively. Increasing taxonomic family richness of arthropod predators and the total number of large (>1 mm) arthropod predators significantly reduced the overwinter survivorship of I. scapularis within the microcosms. Small (<1 mm) arthropod predator abundance had no effect. Our results suggest that forests with complex natural arthropod predator communities show reduced tick survival.

Hypertension prevalence, awareness, treatment and control in the over 50s in Ireland: evidence from The Irish Longitudinal Study on Ageing.

BACKGROUND: To assess the prevalence, awareness, treatment and control of hypertension among adults in Ireland and to describe the determinants of awareness, treatment and control in order to inform public health policy. METHODS: A cross-sectional study of a nationally representative sample of community living adults aged 50 years and older using data collected from 2009 to 2011 for the first wave of the Irish Longitudinal Study on Ageing (TILDA) (n = 5857). Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg and/or currently taking antihypertensive medications. RESULTS: The prevalence of hypertension was 63.7% [95% confidence interval (CI) 62.3-65.1%]. Among those with hypertension, 54.5% (95% CI 52.6-56.2%) were aware of their hypertensive status and 58.9% (95% CI 57.1-60.4%) were on antihypertensive medication. Among those on treatment, 51.6% (95% CI 49.3-53.9%) had their BP controlled to below 140/90 mmHg. Respondents facing financial barriers to primary care and medication were less likely to be on antihypertensive treatment compared with those without financial barriers. CONCLUSIONS: A high prevalence of hypertension was identified in this cohort, with low levels of awareness, treatment and control. Population and primary care interventions are required to reduce prevalence and to improve awareness, detection and management of hypertension.

Antidepressant prescribing in Irish children: secular trends and international comparison in the context of a safety warning.

BACKGROUND: In 2003, the Irish Medicines Board (IMB) warned against the treatment of childhood depression with selective serotonin reuptake inhibitors (SSRIs) due to increased risk of suicide. This study examined the effect of this warning on the prevalence of anti-depressants in Irish children and compared age and gender trends and international comparisons of prescription rates. METHODS: A retrospective cohort study of the Irish Health Service Executive (HSE) pharmacy claims database for the General Medical Services (GMS) scheme for dispensed medication. Data were obtained for 2002-2011 for those aged ≤ 15 years. Prevalence of anti-depressants per 1000 eligible population, along with 95% confidence intervals, were calculated. A negative binomial regression analysis was used to investigate trends and compare rates across years, sex and age groups (0-4, 5-11, 12-15 years). International prescribing data were retrieved from the literature. RESULTS: The prevalence of anti-depressants decreased from 4.74/1000 population (95% CI: 4.47-5.01) in 2002 to 2.61/1000 population (95% CI: 2.43-2.80) in 2008. SSRI rates decreased from 2002 to 2008. Prescription rates for contra-indicated SSRIs paroxetine, sertraline and citralopram decreased significantly from 2002 to 2005, and, apart from paroxetine, only small fluctuations were seen from 2005 onwards. Fluoxetine was the most frequently prescribed anti-depressant and rates increased between 2002 and 2011. Anti-depressant rates were higher for younger boys and older girls. The Irish prevalence was lower than the US, similar to the U.K. and higher than Germany and Denmark. CONCLUSIONS: The direction and timing of these trends suggest that medical practitioners followed the IMB advice.

Recovery from disturbance requires resynchronization of ecosystem nutrient cycles.

Nitrogen (N) and phosphorus (P) are tightly cycled in most terrestrial ecosystems, with plant uptake more than 10 times higher than the rate of supply from deposition and weathering. This near-total dependence on recycled nutrients and the stoichiometric constraints on resource use by plants and microbes mean that the two cycles have to be synchronized such that the ratio of N:P in plant uptake, litterfall, and net mineralization are nearly the same. Disturbance can disrupt this synchronization if there is a disproportionate loss of one nutrient relative to the other. We model the resynchronization of N and P cycles following harvest of a northern hardwood forest. In our simulations, nutrient loss in the harvest is small relative to postharvest losses. The low N:P ratio of harvest residue results in a preferential release of P and retention of N. The P release is in excess of plant requirements and P is lost from the active ecosystem cycle through secondary mineral formation and leaching early in succession. Because external P inputs are small, the resynchronization of the N and P cycles later in succession is achieved by a commensurate loss of N. Through succession, the ecosystem undergoes alternating periods of N limitation, then P limitation, and eventually co-limitation as the two cycles resynchronize. However, our simulations indicate that the overall rate and extent of recovery is limited by P unless a mechanism exists either to prevent the P loss early in succession (e.g., P sequestration not stoichiometrically constrained by N) or to increase the P supply to the ecosystem later in succession (e.g., biologically enhanced weathering). Our model provides a heuristic perspective from which to assess the resynchronization among tightly cycled nutrients and the effect of that resynchronization on recovery of ecosystems from disturbance.

Intercellular adhesion molecule-1 (ICAM-1) is upregulated in aggressive papillary thyroid carcinoma.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is implicated in carcinogenesis. In this study we examined the expression of ICAM-1 in papillary thyroid cancer (PTC). We hypothesized that ICAM-1 correlates with indicators of tumor aggressiveness in PTC. METHODS: Thirty-five primary and metastatic PTCs, five follicular adenomas, five Hashimoto thyroiditis, five nodular hyperplasia, and eight normal thyroid tissue samples were analyzed for ICAM-1 gene expression using quantitative reverse-transcription polymerase chain reaction (RT-PCR). ICAM-1 gene expression was analyzed at protein level by immunohistochemistry (IHC) using a semiquantitative score. Gene expression and intensity levels were correlated with markers of tumor aggressiveness including BRAF V600E mutation, tumor size, extrathyroidal extension (ETE), angiolymphatic invasion, and lymph node metastasis. RESULTS: ICAM-1 gene expression was higher in PTC (p = 0.01) and lymph node metastases (p = 0.03) when compared with benign tumors and Hashimoto's. Furthermore, PTCs exhibiting BRAF V600E mutation (p = 0.01), ETE (p < 0.01), and lymph node metastasis (p = 0.02) were associated with higher ICAM-1 levels. Gene expression correlated with protein levels on IHC. Additionally, poorly differentiated thyroid carcinoma had a higher ICAM-1 intensity score compared with well-differentiated carcinoma (p = 0.03). CONCLUSIONS: ICAM-1 expression is upregulated in papillary thyroid carcinoma. Furthermore, ICAM-1 upregulation correlated with aggressive tumor features such as BRAF V600E mutation, ETE, and lymph node metastasis, suggesting that ICAM-1 plays a role in thyroid cancer progression.

Antibiotic prescribing trends in a paediatric sub-population in Ireland.

PURPOSE: Little is known about antibiotic prescribing in Irish children. This study aims to examine antibiotic prescribing patterns in Irish children and associated costs and to compare this with European findings. METHODS: A retrospective analysis of the Irish Health Services Executive (HSE) pharmacy claims database 2004-2009 for the General Medical Services (GMS) scheme for dispensed medications. This represents 28% of Irish children but over-represents lower socio-economic groups. Overall prescribing rates were reported over time (2004-2009), age (0-4, 5-11, 12-15 years) and gender. Statistical comparison is made using negative binomial regression. Overall prescribing rates for the most commonly prescribed drugs were calculated. Associated cost of prescribing also was calculated. European prescribing data were retrieved from the literature. RESULTS: Rates remained stable from 2004 (631/1000 GMS population; 95%CI 628-634) to 2009 (621/1000; 95%CI 618-624). An interaction effect emerged between gender and age. Rates were generally higher for girls, except for the boys aged 0-4 years. The preferred choice of agents changed across years, with co-amoxiclav becoming the most prescribed drug in 2009 (308/1000; 95%CI 306-310). The total cost of antibiotics increased from €4.4 million in 2004 to €6.0 million in 2009. Higher overall rates of antibiotic prescribing emerged compared with available European data. Differences were observed between prescribing of some first-line and second-line drugs. CONCLUSIONS: Age and gender trends are consistent with international literature. However, Ireland has higher overall prescribing rates relative to some European countries. This suggests that a quality improvement in prescribing intervention is warranted.

AQP-1 association with body fluid loss in 10-km runners.

Intrinsic body fluid regulation is critical for optimizing endurance performance. Aquaporins (AQPs) are a family of transmembrane proteins that transport water and glycerol across cellular membranes. A recent report revealed an association between a single nucleotide polymorphism (SNP) in the 3' untranslated region of the aquaporin-1 (AQP1) gene and endurance performance. The purpose of the study was to explore the association between the AQP1 SNP and acute body fluid loss in long distance runners. The subjects (N=91, Age=26±3 yrs; Ht=170±11 cm; Wt=61±5 kg; mean±SD) were biologically unrelated male long distance runners. Data were collected before and after an international 10 km road race. Body fluid loss was determined by the difference between nude body weight before and after the 10 km run. The AQP1 (G→C) gene variation was detected by the ARMS-PCR procedure. Genotypes were determined by PCR product size. Carriers of the AQP1 SNP had a significantly greater adjusted body fluid loss (3.7±0.9 kg) than non-carriers (1.5±1.1 kg) (P<0.05). In conclusion, our study found an association between the AQP1 SNP and acute body fluid loss in long distance runners.

Human keratinocyte growth factor effects in a porcine model of epidermal wound healing.

Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family (hence the alternative designation FGF-7). It is produced by stromal cells, but acts as a mitogen for epithelial cells. We examined the effects of topically applied KGF on healing of wounds in a porcine model. In partial-thickness wounds, KGF stimulated the rate of reepithelialization (p < 0.0002), associated with a thickening of the epidermis (p < 0.0001). Epidermis from KGF-treated full-thickness wound sites was significantly thicker (0.31 +/- 0.22 mm) compared with mirror image control sites (0.18 +/- 0.12 mm) (p < 0.0001). Moreover, the majority (77%) of KGF-treated wounds exhibited epidermis with a deep rete ridge pattern as compared with control sites. These effects were observed as early as 14 d and persisted for at least 4 wk. KGF treatment also increased the number of serrated basal cells associated with increased deposition of collagen fibers in the superficial dermis adjacent to the acanthotic epidermis. Electron microscopy revealed better developed hemidesmosomes associated with thicker bundles of tonofilaments in the serrated cells. The pattern of epidermal thickening observed in KGF-treated wounds resembled psoriasis. Psoriasis is a disease associated with epidermal thickening, parakeratosis as well as hyperproliferation that extends beyond the basal layer. In striking contrast to psoriasis, KGF-treated wounds exhibited normal orthokeratotic maturation, and proliferation was localized to the basal cells. Our present findings have significant implications concerning the role of KGF as a paracrine modulator of epidermal proliferation and differentiation.

Diagnostic accuracy systematic review of rectal bleeding in combination with other symptoms, signs and tests in relation to colorectal cancer.

BACKGROUND: Rectal bleeding is a recognised early symptom of colorectal cancer. This study aimed to assess the diagnostic accuracy of symptoms, signs and diagnostic tests in patients with rectal bleeding in relation to risk of colorectal cancer in primary care. METHODS: Diagnostic accuracy systematic review. Medline (1966 to May 2009), Embase (1988 to May 2009), British Nursing Index (1991 to May 2009) and PsychINFO (1970 to May 2009) were searched. We included cohort studies that assessed the diagnostic utility of rectal bleeding in combination with other symptoms, signs and diagnostic tests in primary care. An eight-point quality assessment tool was produced to assess the quality of included studies. Pooled positive likelihood ratios (PLRs), sensitivities and specificities were calculated. RESULTS: Eight studies incorporating 2323 patients were included. Average weighted prior probability of colorectal cancer was 7.0% (range: 3.3-15.4%, median: 8.1%). Age > or = 60 years (pooled PLR: 2.79, 95% confidence interval (CI) 2.00-3.90), weight loss (pooled PLR: 1.89, 95% CI: 1.03-3.07) and change in bowel habit (pooled PLR: 1.92, 95% CI: 0.54-3.57) raise the probability of colorectal cancer into the range of referral to secondary care but do not conclusively 'rule in' the diagnosis. Presence of severe anaemia has the highest diagnostic value (pooled PLR: 3.67, 95% CI: 1.30-10.35), specificity 0.95 (95% CI: 0.93-0.96), but still only generates a post-test probability of 21.6%. CONCLUSIONS: In patients with rectal bleeding who present to their general practitioner, additional 'red flag' symptoms have modest diagnostic value. These findings have implications in relation to recommendations contained in clinical practice guidelines.

Shock and tissue injury induced by recombinant human cachectin.

Cachectin (tumor necrosis factor), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. Recombinant human cachectin was infused into rats in an effort to determine whether cachectin, by itself, can elicit the derangements of host physiology caused by administration of endotoxin. When administered in quantities similar to those produced endogenously in response to endotoxin, cachectin causes hypotension, metabolic acidosis, hemoconcentration, and death within minutes to hours, as a result of respiratory arrest. Hyperglycemia and hyperkalemia were also observed after infusion. At necropsy, diffuse pulmonary inflammation and hemorrhage were apparent on gross and histopathologic examination, along with ischemic and hemorrhagic lesions of the gastrointestinal tract, and acute renal tubular necrosis. Thus, it appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.

Association between allopurinol and mortality in heart failure patients: a long-term follow-up study.

AIMS: The aim of the study was to explore the long-term effect of allopurinol on mortality and cardiovascular hospitalisations in heart failure (HF) patients. METHODS: This is a population-based cohort study using a record-linkage database in Tayside, Scotland. A total of 4785 HF patients (4260 non-users, 267 incident users and 258 prevalent users) were studied between 1993 and 2002. RESULTS: Compared with non-users, low-dose users in the incident group had a significant increased risk of all-cause mortality, cardiovascular mortality and cardiovascular recurrence (adjusted HR, 1.60, 95%CI 1.26-2.03; 1.70, 1.29-2.23 and 1.44, 1.01-2.07). For the prevalent users, the adjusted HR were 1.27, 0.98-1.64; 1.43, 1.07-1.90 and 1.27, 0.91-1.76 respectively. There was no increased risk of outcome for high-dose users when compared with non-users (adjusted HR, 1.18, 0.84-1.66; 1.14, 0.76-1.71 and 1.36, 0.88-2.10 for the incident users, and 0.86, 0.64-1.15; 0.90, 0.64-1.26; and 1.27, 0.93-1.74 for the prevalent users respectively). High-dose allopurinol was associated with reduced risk of all-course mortality for prevalent users when compared with low-dose (adjusted HR 0.65, 95%CI 0.42-0.99). CONCLUSIONS: The prevalent high-dose allopurinol use had a lower risk of mortality than the prevalent low-dose use suggesting that allopurinol may be of benefit in HF patients.

Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer.

Increasing duration of tamoxifen therapy improves survival in women with breast cancer but the impact of adherence to tamoxifen on mortality is unclear. This study investigated whether women prescribed tamoxifen after surgery for breast cancer adhered to their prescription and whether adherence influenced survival. A retrospective cohort study of all women with incident breast cancer in the Tayside region of Scotland between 1993 and 2002 was linked to encashed prescription records to calculate adherence to tamoxifen. Survival analysis was used to determine the effect of adherence on all-cause mortality. In all 2080 patients formed the study cohort with 1633 (79%) prescribed tamoxifen. The median duration of use was 2.42 years (IQR=1.04-4.89 years). Longer duration was associated with better survival but this varied over time. The hazard ratio for mortality in relation to duration at 2.4 years was 0.85, 95% CI=0.83-0.87. Median adherence to tamoxifen was 93% (interquartile range=84-100%). Adherence <80% was associated with poorer survival, hazard ratio 1.10, 95% CI=1.001-1.21. Persistence with tamoxifen was modest with only 49% continuing therapy for 5 years of those followed up for 5 years or more. Increased duration of tamoxifen reduces the risk of death, although one in two women do not complete the recommended 5-year course of treatment. A significant proportion of women have low adherence to tamoxifen and are at increased risk of death.

Nitrogen retention in urban lawns and forests.

Lawns are a dominant cover type in urban ecosystems, and there is concern about their impacts on water quality. However, recent watershed-level studies suggest that these pervious areas might be net sinks, rather than sources, for nitrogen (N) in the urban environment. A 15N pulse-labeling experiment was performed on lawn and forest plots in the Baltimore (Maryland, U.S.A.) metropolitan area to test the hypothesis that lawns are a net sink for atmospheric-N deposition and to compare and contrast mechanisms of N retention in these vegetation types. A pulse of 15N-NO3-, simulating a precipitation event, was followed through mineral soils, roots, Oi-layer/thatch, aboveground biomass, microbial biomass, inorganic N, and evolved N2 gas over a one-year period. The 15N label was undetectable in gaseous samples, but enrichment of other pools was high. Gross rates of production and consumption of NO3- and NH4+ were measured to assess differences in internal N cycling under lawns and forests. Rates of N retention were similar during the first five days of the experiment, with lawns showing higher N retention than forests after 10, 70, and 365 days. Lawns had larger pools of available NO3- and NH4+; however, gross rates of mineralization and nitrification were also higher, leading to no net differences in NO3- and NH4+ turnover times between the two systems. Levels of 15N remained steady in forest mineral soils from day 70 to 365 (at 23% of applied 15N), but continued to accumulate in lawn mineral soils over this same time period, increasing from 20% to 33% of applied 15N. The dominant sink for N in lawn plots changed over time. Immobilization in mineral soils dominated immediately (one day) after tracer application (42% of recovered 15N); plant biomass dominated the short term (10 days; 51%); thatch and mineral-soil pools together dominated the medium term (70 days; 28% and 36%, respectively); and the mineral-soil pool alone dominated long-term retention (one year; 70% of recovered 15N). These findings illustrate the mechanisms whereby urban and suburban lawns under low to moderate management intensities are an important sink for atmospheric-N deposition.

Over-the-counter medications for acute cough in children and adults in ambulatory settings.

BACKGROUND: Acute cough due to upper respiratory tract infection (URTI) is a common symptom. Non-prescription over-the-counter (OTC) medicines are frequently recommended as a first-line treatment, but there is little evidence as to whether these drugs are effective. OBJECTIVES: To assess the effects of oral OTC cough preparations for acute cough. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4); MEDLINE (January 1966 to January Week 1, 2007); EMBASE (January 1974 to January 2007); and the UK Department of Health National Research Register (June 2007). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral OTC cough preparations with placebo in children and adults suffering from acute cough in ambulatory settings. We considered all cough outcomes and second outcomes of interest were adverse effects. DATA COLLECTION AND ANALYSIS: Two review authors independently screened potentially relevant citations and independently extracted data and assessed study quality. Quantitative analysis was performed where appropriate. MAIN RESULTS: Twenty five trials (17 in adults, 8 in children) involving 3492 people (2876 adults and 616 children) were included. RESULTS OF STUDIES IN ADULTS: Six trials compared antitussives with placebo and had variable results. Two trials compared the expectorant, guaifenesin with placebo, one indicated significant benefit whereas the other did not. One trial found that a mucolytic reduced cough frequency and symptom scores. Two studies examined antihistamine-decongestant combinations and found conflicting results. Three studies compared other combinations of drugs with placebo and indicated some benefit in reducing cough symptoms. Three trials found antihistamines were no more effective than placebo in relieving cough symptoms. RESULTS OF STUDIES IN CHILDREN: Antitussives (two studies), antihistamines (two studies), antihistamine decongestants (two studies) and antitussive/bronchodilator combinations (one study) were no more effective than placebo. No studies using expectorants met our inclusion criteria. The results of one trial favoured active treatment with mucolytics over placebo. One trial tested two paediatric cough syrups and both preparations showed a 'satisfactory response' in 46% and 56% of children compared to 21% of children in the placebo group. AUTHORS' CONCLUSIONS: There is no good evidence for or against the effectiveness of OTC medicines in acute cough. The results of this review have to be interpreted with caution due differences in study characteristics and quality. Studies often showed conflicting results with uncertainty regarding clinical relevance. Higher quality evidence is needed to determine the effectiveness of self-care treatments for acute cough.

The accuracy of symptoms, signs and diagnostic tests in the diagnosis of left ventricular dysfunction in primary care: a diagnostic accuracy systematic review.

BACKGROUND: To assess the accuracy of findings from the clinical history, symptoms, signs and diagnostic tests (ECG, CXR and natriuretic peptides) in relation to the diagnosis of left ventricular systolic dysfunction (LVSD) in a primary care setting. METHODS: Diagnostic accuracy systematic review, we searched Medline (1966 to March 2008), EMBASE (1988 to March 2008), Central, Cochrane and ZETOC using a diagnostic accuracy search filter. We included cross-sectional or cohort studies that assess the diagnostic utility of clinical history, symptoms, signs and diagnostic tests, against a reference standard of echocardiography. We calculated pooled positive and negative likelihood ratios and assessed heterogeneity using the I2 index. RESULTS: 24 studies incorporating 10,710 patients were included. The median prevalence of LVSD was 29.9% (inter-quartile range 14% to 37%). No item from the clinical history or symptoms provided sufficient diagnostic information to "rule in" or "rule out" LVSD. Displaced apex beat shows a convincing diagnostic effect with a pooled positive likelihood ratio of 16.0 (8.2-30.9) but this finding occurs infrequently in patients. ECG was the most widely studied diagnostic test, the negative likelihood ratio ranging from 0.06 to 0.6. Natriuretic peptide results were strongly heterogeneous, with negative likelihood ratios ranging from 0.02 to 0.80. CONCLUSION: Findings from the clinical history and examination are insufficient to "rule in" or "rule out" a diagnosis of LVSD in primary care settings. BNP and ECG measurement appear to have similar diagnostic utility and are most useful in "ruling out" LVSD with a normal test result when the probability of LVSD is in the intermediate range.

Supporting prescribing in Irish primary care: protocol for a non-randomised pilot study of a general practice pharmacist (GPP) intervention to optimise prescribing in primary care.

BACKGROUND: Prescribing for patients taking multiple medicines (i.e. polypharmacy) is challenging for general practitioners (GPs). Limited evidence suggests that the integration of pharmacists into the general practice team could improve the management of these patients. The aim of this study is to develop and test an intervention involving pharmacists, working within GP practices, to optimise prescribing in Ireland, which has a mixed public and private primary healthcare system. METHODS: This non-randomised pilot study will use a mixed-methods approach. Four general practices will be purposively sampled and recruited. A pharmacist will join the practice team for 6 months. They will participate in the management of repeat prescribing and undertake medication reviews (which will address high-risk prescribing and potentially inappropriate prescribing, deprescribing and cost-effective and generic prescribing) with adult patients. Pharmacists will also provide prescribing advice regarding the use of preferred drugs, undertake clinical audits, join practice team meetings and facilitate practice-based education. Throughout the 6-month intervention period, anonymised practice-level medication (e.g. medication changes) and cost data will be collected. A nested Patient Reported Outcome Measure (PROM) study will be undertaken during months 4 and 5 of the 6-month intervention period to explore the impact of the intervention in older adults (aged ≥ 65 years). For this, a sub-set of 50 patients aged ≥ 65 years with significant polypharmacy (≥ 10 repeat medicines) will be recruited from each practice and invited to a medication review with the pharmacist. PROMs and healthcare utilisation data will be collected using patient questionnaires, and a 6-week follow-up review conducted. Acceptability of the intervention will be explored using pre- and post-intervention semi-structured interviews with key stakeholders. Quantitative and qualitative data analysis will be undertaken and an economic evaluation conducted. DISCUSSION: This non-randomised pilot study will provide evidence regarding the feasibility and potential effectiveness of general practice-based pharmacists in Ireland and provide data on whether a randomised controlled trial of this intervention is indicated. It will also provide a deeper understanding as to how a pharmacist working as part of the general practice team will affect organisational processes and professional relationships in a mixed public and private primary healthcare system.

Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects.