Parenteral nutrition in patients with renal failure – Guidelines on Parenteral Nutrition, Chapter 17

Partial EN (enteral nutrition) should always be aimed for in patients with renal failure that require nutritional support. Nevertheless PN (parenteral nutrition) may be necessary in renal failure in patient groups with acute or chronic renal failure (ARF or CRF) and additional acute diseases but without extracorporeal renal replacement therapy, or in patients with ARF or CRF with additional acute diseases on extracorporeal renal replacement therapy, haemodialysis therapy (HD), peritoneal dialysis (PD) or continuous renal replacement therapy (CRRT), or in patients on HD therapy with intradialytic PN. Patients with renal failure who show marked metabolic derangements and changes in nutritional requirements require the use of specifically adapted nutrient solutions. The substrate requirements of acutely ill, non-hypercatabolic patients with CRF correspond to those of patients with ARF who are not receiving any renal replacement patients therapy (utilisation of the administered nutrients has to be monitored carefully). In ARF patients and acutely ill CRF patients on renal replacement therapy, substrate requirements depend on disease severity, type and extent/frequency of extracorporeal renal replacement therapy, nutritional status, underlying disease and complications occurring during the course of the disease. Patients under HD have a higher risk of developing malnutrition. Intradialytic PN (IDPN) should be used if causes of malnutrition cannot be eliminated and other interventions fail. IDPN should only be carried out when modifiable causes of malnutrition are excluded and enhanced oral (like i.e. additional energy drinks) or enteral supply is unsuccessful or cannot be carried out

A comparison of random forests, boosting and support vector machines for genomic selection

Genomic selection (GS) involves estimating breeding values using molecular markers spanning the entire genome. Accurate prediction of genomic breeding values (GEBVs) presents a central challenge to contemporary plant and animal breeders. The existence of a wide array of marker-based approaches for predicting breeding values makes it essential to evaluate and compare their relative predictive performances to identify approaches able to accurately predict breeding values. We evaluated the predictive accuracy of random forests (RF), stochastic gradient boosting (boosting) and support vector machines (SVMs) for predicting genomic breeding values using dense SNP markers and explored the utility of RF for ranking the predictive importance of markers for pre-screening markers or discovering chromosomal locations of QTLs

Protocol for the Smoking, Nicotine and Pregnancy (SNAP) trial: double-blind, placebo-randomised, controlled trial of nicotine replacement therapy in pregnancy

Background: Smoking in pregnancy remains a public health challenge. Nicotine replacement therapy (NRT) is effective for smoking cessation in non-pregnant people, but because women metabolise nicotine and cotinine much faster in pregnancy, it is unclear whether this will be effective for smoking cessation in pregnancy. The NHS Health Technology Assessment Programme (HTA)-funded smoking, nicotine and pregnancy ( SNAP) trial will investigate whether or not nicotine replacement therapy ( NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women. Methods/Design: Over two years, in 5 trial centres, 1050 pregnant women who are between 12 and 24 weeks pregnant will be randomised as they attend hospital for ante-natal ultrasound scans. Women will receive either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure is biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date ( defined before randomisation and set within two weeks of this) and delivery. At six months after childbirth self-reported maternal smoking status will be ascertained and two years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial will be compared in both groups. Discussion: This trial is designed to ascertain whether or not standard doses of NRT ( as transdermal patches) are effective and safe when used for smoking cessation during pregnancy

Selected acute phase CSF factors in ischemic stroke: findings and prognostic value

<p>Abstract</p> <p>Background</p> <p>Study aimed at investigation of pathogenic role and prognostic value of several selected cerebrospinal fluid acute phase factors that can reflect the severity of ischemic brain damage.</p> <p>Methods</p> <p>Ninety five acute ischemic stroke patients were investigated. Ischemic region visualized at the twenty fourth hour by conventional Magnetic Resonance Imaging. Stroke severity evaluated by National Institute Health Stroke Scale. One month outcome of disease was assessed by Barthel Index. Cerebrospinal fluid was taken at the sixth hour of stroke onset. CSF pro- and anti-inflammatory cytokines were studied by Enzyme Linked Immunosorbent Assay. Nitric Oxide and Lipoperoxide radical were measured by Electron Paramagnetic Resonance. CSF Nitrate levels were detected using the Griess reagent. Statistics performed by SPSS-11.0.</p> <p><b>Results</b></p> <p>At the sixth hour of stroke onset, cerebrospinal fluid cytokine levels were elevated in patients against controls. Severe stroke patients had increased interleukin-6 content compared to less severe strokes (P < 0.05). Cerebrospinal fluid Electron Paramagnetic Resonance signal of nitric oxide was increased in patients against controls. Severe stroke group had an elevated Electron Paramagnetic Resonance signal of lipoperoxiradical compared to less severe stroke. Cerebrospinal fluid nitrate levels in less severe stroke patients were higher than those for severe stroke and control. Positive correlation was established between the initial interleukin-6 content and ischemic lesion size as well as with National Institute Health Stroke Scale score on the seventh day. Initial interleukin-6 and nitrate levels in cerebrospinal fluid found to be significant for functional outcome of stroke at one month.</p> <p><b>Conclusion</b></p> <p>According to present study the cerebrospinal fluid contents of interleukin-6 and nitrates seem to be the most reliable prognostic factors in acute phase of ischemic stroke.</p

Colon cancer risk and different HRT formulations: a case-control study

<p>Abstract</p> <p>Background</p> <p>Most studies have found no increased risk of colon cancer associated with hormone replacement therapy (HRT), or even a decreased risk. But information about the effects of different HRT preparations is lacking.</p> <p>Methods</p> <p>A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched to each case of colon cancer. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Stratified analyses were performed to get an impression of the risk associated with different estrogens and progestins.</p> <p>Results</p> <p>A total of 354 cases of colon cancer were compared with 1422 matched controls. The adjusted overall risk estimate for colon cancer (ColC) associated with ever-use of HRT was 0.97 (0.71 – 1.32). No clinically relevant trends for ColC risk were observed with increasing duration of HRT use, or increasing time since first or last HRT use in aggregate.</p> <p>Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT preparation groups (estrogens and progestins) were too small for conclusions. Nevertheless, if the ColC risk estimates are taken at face value, most seemed to be reduced compared with never-use of HRT, but did not vary much across HRT formulation subgroups. In particular, no substantial difference in ColC risk was observed between HRT-containing conjugated equine estrogens (CEE) or medroxyprogesterone acetate (MPA) and other formulations more common in Europe.</p> <p>Conclusion</p> <p>Ever-use of HRT was not associated with an increased risk of colon cancer. In contrary, most risk estimates pointed non-significantly toward a lower ColC risk in HRT ever user. They did not vary markedly among different HRT formulations (estrogens, progestins). However, the small numbers and the overlapping nature of the subgroups suggest cautious interpretation.</p

Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron

Twenty Years of Hepatitis C in the Treviso District (Local Health Unit 2): Treatments, Clinical Management and Cost Analysis

Chronic hepatitis C virus (HCV) infection is a global health problem, and about 10-30% of patients develop cirrhosis or hepatocellular carcinoma several years after being infected. In past decades, treatment of HCV infection was based on peginterferon and ribavirin, which lead to a sustained virologic response (SVR) in only 50-60% of patients. Since 2014, direct acting antiviral (DAA) agents have been available. Patients administered DAA agents usually reach SVR in 12 weeks. The aim of this study was to estimate the cost analysis of these innovative drugs while also taking into account the total health expenditure for managing HCV infection. The pharmaceutical and hospitalisation databases of the Local Health Unit (ULSS2) of Treviso were retrospectively analysed between 1997 and 2016 for each HCV patient. During this twenty-year period, people affected by HCV totalled 2,949; 277 of these patients were treated with DAA and, of these, only 2% did not reach SVR. The HCV genotype 1b was the most common, accounting for 58% of the total patients. The treatment for HCV genotype 3 was associated with higher costs. The expenses for the new treatments were found to be significantly higher compared to those for the old ones (i.e., peginterferon and ribavirin). The average costs for a cycle of therapy were €8,000 and €24,000 for interferon and DAA therapy, respectively. Total health care costs associated with HCV (excluding DAA treatments) for an individual HCV infection patient were estimated to be €32,000. Our results confirm the high efficacy of DAA therapy. Furthermore, these agents improve the clinical conditions and reduce both the treatment cost and health care in patients with HCV infection

Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study

Background: The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk. / Methods: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies. / Findings: We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from 66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% [3–9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3–12) of males to be at high risk compared with 3% (2–7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease. / Interpretation: About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds

Contrasting Biogeographic and Diversification Patterns in Two Mediterranean-Type Ecosystems

The five Mediterranean regions of the world comprise almost 50,000 plant species (ca 20% of the known vascular plants) despite accounting for less than 5% of the world’s land surface. The ecology and evolutionary history of two of these regions, the Cape Floristic Region and the Mediterranean Basin, have been extensively investigated, but there have been few studies aimed at understanding the historical relationships between them. Here, we examine the biogeographic and diversification processes that shaped the evolution of plant diversity in the Cape and the Mediterranean Basin using a large plastid data set for the geophyte family Hyacinthaceae (comprising ca. 25% of the total diversity of the group), a group found mainly throughout Africa and Eurasia. Hyacinthaceae is a predominant group in the Cape and the Mediterranean Basin both in terms of number of species and their morphological and ecological variability. Using state-of-the-art methods in biogeography and diversification, we found that the Old World members of the family originated in sub-Saharan Africa at the Paleocene–Eocene boundary and that the two Mediterranean regions both have high diversification rates, but contrasting biogeographic histories. While the Cape diversity has been greatly influenced by its relationship with sub-Saharan Africa throughout the history of the family, the Mediterranean Basin had no connection with the latter after the onset of the Mediterranean climate in the region and the aridification of the Sahara. The Mediterranean Basin subsequently contributed significantly to the diversity of neighbouring areas, especially Northern Europe and the Middle East, whereas the Cape can be seen as a biogeographical cul-de-sac, with only a few dispersals toward sub-Saharan Africa. The understanding of the evolutionary history of these two important repositories of biodiversity would benefit from the application of the framework developed here to other groups of plants present in the two regions