Mortality among patients who receive or defer gastrostomies.

BACKGROUND & AIMS: There are few data on outcomes and mortality of patients who have received gastrostomies. We assessed 30-day and 1-year mortalities of patients in the United Kingdom who were referred to hospitals for gastrostomies and of patients who deferred this intervention. METHODS: We collected data from 1327 patients referred to 2 hospitals in Sheffield, United Kingdom, for gastrostomies from February 2004 through May 2010. Data were analyzed to determine 30-day and 1-year mortalities. Predicted mortality by using the validated Sheffield Gastrostomy Scoring System (SGSS) was then compared with actual mortality by using area under the receiver operator curves to determine levels of agreement in patients referred for gastrostomy. RESULTS: Three hundred four patients (23%) did not undergo gastrostomy after multidisciplinary team discussion, which was based on physicians' recommendations. This group had 35.5% mortality at 30 days and 74.3% at 1 year, whereas mortality among patients who underwent gastrostomy (n = 1027) was 11.2% at 30 days and 41.1% at 1 year (P < .0001, compared with patients who deferred the procedure). The area under the receiver operator curves for the SGSS demonstrated acceptable agreement between predicted and actual mortality in patients who underwent or were deferred gastrostomy. CONCLUSIONS: On the basis of data from 1327 patients, those who undergo gastrostomy have significantly lower mortality than those who defer the procedure. Without applying the SGSS, clinicians are able to select patients most likely to benefit from gastrostomy. The SGSS could provide objective support to clinicians involved in making ethically contentious or potentially litigious decisions.

Albumin level and patient age predict outcomes in patients referred for gastrostomy insertion: internal and external validation of a gastrostomy score and comparison with artificial neural networks.

BACKGROUND: Significant mortality after gastrostomy insertion remains and some risk factors have been identified, but no predictive scoring system exists. OBJECTIVE: To identify risk factors for mortality, formulate a predictive scoring system, and validate the score. Comparison to an artificial neural network (ANN). DESIGN: Endoscopic database analysis. SETTING: Six hospitals (2 teaching hospitals) in the South Yorkshire region, United Kingdom. PATIENTS: This study involved all patients referred for gastrostomy insertion. INTERVENTION: Generation of clinical scores to predict 30-day mortality in patients undergoing gastrostomy insertion. MAIN OUTCOME MEASUREMENTS: Risk factors for 30-day mortality. Internal and external validation of the score. Comparison with an ANN. RESULTS: Univariate analysis showed that 30-day mortality was associated with age, albumin levels, and cardiac and neurological comorbidities. Multivariate analysis showed that only age and albumin levels were independent. Modeling provided scores of 0, 1, 2, and 3 corresponding to 30-day mortalities of 0% (0-2.1), 7% (2.9-13.9), 21.3% (13.5-30.9), and 37.3% (24.1-51.9), respectively. Application of the scoring system at the other teaching hospital and the 4 district general hospitals gave 30-day mortality rates that were not significantly different from those predicted. Receiver operating characteristic curves for the score and the ANN were comparable. LIMITATIONS: Nonrandomized study. Score not used as a decision-making tool. CONCLUSION: The gastrostomy score provides an estimate of 30-day mortality for patients (and their relatives) when gastrostomy insertion is being discussed. This score requires evaluation as a decision-making tool in clinical practice. ANN analysis results were similar to the outcomes from the clinical score.

Study protocol for randomised clinical trial comparing the effectiveness of side-lying sleep positioning to back-lying at reducing oxygen desaturation resulting from obstructive sleep apnoea in infants with cleft palate (SLUMBRS2).

INTRODUCTION: The craniofacial abnormalities found in infants with cleft palate (CP) decrease their airway patency and increase their risk of obstructive sleep apnoea (OSA). We hypothesise that optimising sleep position in infants with CP may improve airway patency and offer a 'low-cost, high-impact' intervention to prevent the negative impacts of OSA. Because cleft centres give inconsistent advice about sleep position: some recommend back-lying and others side-lying, we will compare these in a randomised controlled trial. METHODS AND ANALYSIS: The aim is to determine the clinical effectiveness of side-lying as compared with back-lying sleep positioning in terms of reducing oxygen desaturation resulting from OSA in 244 infants aged 3-5 weeks of age, diagnosed with an isolated CP in/by UK cleft centres. Primary outcome is the 4% Oxygen Desaturation Index measured using pulse oximetry during sleep. RESEARCH PLAN: 1. Multicentre randomised controlled trial of side-lying compared with back-lying sleep positioning in reducing oxygen desaturation resulting from OSA in infants with CP at one month of age. 2. Internal pilot questionnaire-based study to support parents and clinicians regarding study participation, seeking to identify and address any barriers to recruitment. Monitoring data from the internal pilot will be used in the final analysis. 3. Co-development of new UK recommendations with Cleft Lip and Palate Association (CLAPA) regarding sleep position for infants with CP. ETHICS AND DISSEMINATION: The study protocol has received the favourable opinion of the West Midlands-South Birmingham Research Ethics Committee. Study results will be published on affiliated webpages and in peer-reviewed publications and conference contributions. TRIAL REGISTRATION NUMBER: NCT04478201.

Iodothyronine deiodinase enzyme activities in bone.

Euthyroid status is essential for normal skeletal development and maintenance of the adult skeleton, but the mechanisms which control supply of thyroid hormone to bone cells are poorly understood. Thyroid hormones enter target cells via monocarboxylate transporter-8 (MCT8), which provides a functional link between thyroid hormone uptake and metabolism in the regulation of T3-action but has not been investigated in bone. Most circulating active thyroid hormone (T3) is derived from outer ring deiodination of thyroxine (T4) mediated by the type 1 deiodinase enzyme (D1). The D2 isozyme regulates intra-cellular T3 supply and determines saturation of the nuclear T3-receptor (TR), whereas a third enzyme (D3) inactivates T4 and T3 to prevent hormone availability and reduce TR-saturation. The aim of this study was to determine whether MCT8 is expressed in the skeleton and whether chondrocytes, osteoblasts and osteoclasts express functional deiodinases. Gene expression was analyzed by RT-PCR and D1, D2 and D3 function by sensitive and highly specific determination of enzyme activities. MCT8 mRNA was expressed in chondrocytes, osteoblasts and osteoclasts at all stages of cell differentiation. D1 activity was undetectable in all cell types, D2 activity was only present in mature osteoblasts whereas D3 activity was evident throughout chondrocyte, osteoblast and osteoclast differentiation in primary cell cultures. These data suggest that T3 availability especially during skeletal development may be limited by D3-mediated catabolism rather than by MCT8 mediated cellular uptake or D2-dependent T3 production.

Decoupling the direct and indirect effects of nitrogen deposition on ecosystem function.

Elevated nitrogen (N) inputs into terrestrial ecosystems are causing major changes to the composition and functioning of ecosystems. Understanding these changes is challenging because there are complex interactions between 'direct' effects of N on plant physiology and soil biogeochemistry, and 'indirect' effects caused by changes in plant species composition. By planting high N and low N plant community compositions into high and low N deposition model terrestrial ecosystems we experimentally decoupled direct and indirect effects and quantified their contribution to changes in carbon, N and water cycling. Our results show that direct effects on plant growth dominate ecosystem response to N deposition, although long-term carbon storage is reduced under high N plant-species composition. These findings suggest that direct effects of N deposition on ecosystem function could be relatively strong in comparison with the indirect effects of plant community change.

Survival analysis after gastrostomy: a single-centre, observational study comparing radiological and endoscopic insertion.

OBJECTIVES: Percutaneous endoscopic gastrostomy (PEG) using the pull through technique is the most widely used insertion method. An alternative is a per-oral image-guided gastrostomy (PIG), which may be advantageous in high-risk patients. As there are no large studies comparing PEG against PIG, we wished to analyse mortality after endoscopic or radiological gastrostomy insertion. METHODS: Patients referred for a gastrostomy are prospectively included in a database along with demographic, biochemical and outcome data. Analysis of gastrostomy insertions from February 2004 to 2007 was performed with reference to method of insertion and 30-day outcome. Patients were subgrouped into cognitive impairment, dysphagic stroke, oropharygeal cancer, neurological cancer and other. RESULTS: One hundred and seventy PIGs and 233 PEGs were inserted (mean age 62 years, 268 males). There were no differences in age between the PIG and the PEG group. The PIG 30-day mortality was 26 of 170 (15.3%) and the PEG 30-day mortality was 25 of 233 (10.7%) (P=0.17). One-year mortality was 92 of 170 (54.1%) for PIG and 131 of 233 (56.7%) for PEG (P=0.60). Subgroup analysis revealed higher 30-day mortality in patients with nasopharyngeal cancer undergoing PIG; 14 of 106 (13.2%) versus one of 69 (1.4%) (P=0.005). However, PIG patients were older than PEG patients (mean age 64 vs. 59.7 years, P=0.019) and had more comorbidities (21.1% in the PEG group and 37.7% in the PIG group). CONCLUSION: Overall PIG and PEG seem to have similar 30-day and 1-year mortality rates. Our data suggest that clinicians may opt for either approach depending on technical considerations and local availability.

Interactions between GH, IGF-I, glucocorticoids, and thyroid hormones during skeletal growth.

Linear growth occurs during development and the childhood years until epiphyseal fusion occurs. This process results from endochondral ossification in the growth plates of long bones and is regulated by systemic hormones and paracrine or autocrine factors. The major regulators of developmental and childhood growth are GH, IGF-I, glucocorticoids, and thyroid hormone. Sex steroids are responsible for the pubertal growth spurt and epiphyseal fusion. This review will consider interactions between GH, IGF-I, glucocorticoids, and thyroid hormone during linear growth. It is well known from physiologic and clinical studies that these hormones interact at the level of the hypothalamus and pituitary. Interacting effects on peripheral tissues such as liver are also well understood, but we concentrate here on the epiphyseal growth plate as an important and newly appreciated target organ for convergent hormone action.