Higher Incidence Of Diarrhea Research Articles

Infectious diarrhea in autologous stem cell transplantation: high prevalence of coccidia in a South American center

BackgroundDiarrhea is frequently seen in autologous stem cell transplantation. Although toxicity related to conditioning is the most common cause, infectious pathogens can play a distinctive role particularly in certain regions and environments. MethodsThe role of enteropathogens was investigated in 47 patients submitted to autologous stem cell transplantation at a Brazilian center between May 2011 and May 2013. All patients who presented with diarrhea consented to stool sample analysis to identify the etiological agents including coccidia, Strongyloides sp., Clostridium difficile and other pathogenic bacteria. ResultsThirty-nine patients (83%) had diarrhea, among whom seven (17.5%) presented with coccidia, three (7.5%) with Candida sp., one (2.5%) with C. difficile, and one (2.5%) with Giardia lamblia. There was a tendency toward a higher incidence of diarrhea in older patients (p-value=0.09) and those who received conditioning with lomustine, etoposide, cytarabine, and melphalan (p-value=0.083). Furthermore, the number of days of neutropenia was higher in patients with diarrhea (p-value=0.06). ConclusionsThe high frequency of diarrhea caused by coccidia shows the importance of investigating and correctly identifying etiological agents and highlights the possible varieties of intestinal infections in patients who undergo autologous stem cell transplantation.

Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in HER3-positive, HER2-low metastatic breast cancer

SummaryPurpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m2 weekly in all cohorts). Patients in Cohort 3 received prophylactic loperamide treatment. Results Diarrhea grade 3 was a dose-limiting toxicity of Cohort 1 defining the maximum tolerated dose of lumretuzumab when given in combination with pertuzumab and paclitaxel at 500 mg every three weeks. Grade 3 diarrhea decreased from 50% (Cohort 2) to 30.8% (Cohort 3) with prophylactic loperamide administration and omission of the pertuzumab LD, nonetheless, all patients still experienced diarrhea. In first-line MBC patients, the objective response rate in Cohorts 2 and 3 was 55% and 38.5%, respectively. No relationship between HER2 and HER3 expression or somatic mutations and clinical response was observed. Conclusions Combination treatment with lumretuzumab, pertuzumab and paclitaxel was associated with a high incidence of diarrhea. Despite the efforts to alter dosing, the therapeutic window remained too narrow to warrant further clinical development. Trial registration: on ClinicalTrials.gov with the identifier NCT01918254 first registered on 3rd July 2013.

P197 Incidence and management of immunotherapy-induced colitis in a tertiary melanoma and IBD centre: Clinical practice data

Checkpoint inhibitors are a novel anti-cancer therapy that are standard of care in metastatic melanoma, non-small cell lung and renal cancer.1 CTLA-4 inhibitors (e.g. Ipilimumab) and PD-1 inhibitors (Nivolumab, Pembrolizumab) can be used separately or in combination for melanoma. Their immune inhibition is non-specific, leading to a number of immune-related adverse events (irAEs) including colitis, hepatitis and pancreatitis.2 Combination therapy is known to cause more irAEs than single-agent CTLA-4 inhibition. There are limited real-world clinical data describing the incidence and management of these GI irAEs. The aims this study were (1) To determine the incidence of GI irAEs in a tertiary oncology centre and (2) to analyse the management and outcome of GI irAEs within a tertiary oncology and IBD centre. Retrospective single–centre review. Melanoma patients receiving Ipilimumab ± Nivolumab between Dec 2011 and June 2017 were identified from the oncology prescribing database. The electronic patient record (EPR) was used to determine the incidence of GI side effects. Investigations, treatment, and outcome data were collated. 153 patients who received immunotherapy were identified. There was a higher incidence of diarrhoea and hepatitis (n = 21/28,75%) in those receiving dual therapy vs. monotherapy (n = 25/115,22%). Flowchart of patient outcomes. Venn diagram demonstrates actual numbers with colitis (defined as diarrhoea of any grade), hepatitis or both The incidence of diarrhoea for dual therapy (n = 18/28,64%) was in excess of that described in trial data (44%) [3] . Diarrhoea incidence for CTLA-4 inhibition was similar to published data (20% vs. 33%3). Dual therapy resulted in more frequent use of infliximab (22%) vs. monotherapy (15%). Colitis was generally associated with a raised CRP and low albumin. There was significant variability in symptoms, time of onset, and in management decisions. Dual therapy with CTLA-4 and PD-1 inhibitors may result in a higher incidence of colitis than described in clinical trials. Although guidelines exist [2] , there is no clear biological threshold for timing of therapy initiation and escalation, resulting in variability in care. This case series demonstrates that irAE colitis is a common problem that has implications for healthcare provision and care standardisation. Complete management and outcome data will be presented. 1. Gupta A, et al. Systematic review: colitis associated with anti-CTLA-4 therapy. Aliment Pharmacol Ther 2015;42:406–417. 2. Cheng R, et al. Ipilimumab-induced toxicities and the gastroenterologist. J Gastroenterol Hepatol 2015;30:657–666. 3. Larkin J, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Eng J Med 2015;373:23–34.

Dacomitinib-induced diarrhea: Targeting chloride secretion with crofelemer.

Dacomitinib, an irreversible small-molecule pan-ErbB TKI, has a high incidence of diarrhea, which has been suggested to be due to chloride secretory mechanisms. Based on this hypothesis, crofelemer, an antisecretory agent may be an effective intervention. T84 monolayers were treated with 1 µM dacomitinib and 10 µM crofelemer, and mounted into Ussing chambers for electrogenic ion analysis. Crofelemer attenuated increases in chloride secretion in cells treated with dacomitinib. Albino Wistar rats (n = 48) were treated with 7.5 mg/kg dacomitinib and/or 25 mg/kg crofelemer via oral gavage for 21 days. Crofelemer significantly worsened dacomitinib-induced diarrhea (p = 0.0003), and did not attenuate weight loss (p < 0.0001). Sections of the ileum and colon were mounted into Ussing chambers, and secretory processes analyzed. This indicated that crofelemer lost its anti-secretory action in the presence of dacomitinib in this model. Mass spectrometry revealed that crofelemer did not change serum concentration of dacomitinib. Serum FITC dextran levels indicated that crofelemer was unable to attenuate dacomitinib-induced barrier dysfunction. Tight junction proteins were visualized with immunofluorescence. Qualitative analysis showed dacomitinib induced proteolysis of ZO-1 and occludin, and internalization of claudin-1, which was not attenuated by crofelemer. Detailed histopathological analysis showed that crofelemer was unable to attenuate dacomitinib-induced ileal damage. Crofelemer worsened dacomitinib-induced diarrhea, suggesting that antisecretory drug therapy may be ineffective in this setting.

Germination of faba beans (Vicia faba L.) for organic weaning piglets

Faba beans (Vicia faba L.) contain anti-nutritive compounds that can reduce digestibility and palatability. Germination has been reported to reduce some of those components. The effect of including germinated faba beans in their feed was tested on 160 weaner pigs that were assigned to one of four diets containing either 19% peas (RP19), 16% raw faba beans (RFB16), 16% germinated faba beans (GFB16) or 24% germinated faba beans (GFB24). Crude protein was slightly higher in germinated as compared to raw beans. Most of the essential amino acids decreased due to germination, their contents relative to lysine remained the same. There were no significant differences in live weight on days 8, 15 and 22. At the end of the trial (day 29), live weight of GFB24 was significantly reduced when compared to RP19 and RFB16, but not to GFB16. In week 4, daily weight gain of GFB24 was significantly lower than of all other treatments. There were no significant differences in feed intake between the treatments. It was possible to feed germinated faba bean in amounts up to 240 g kg FM−1 without a reduction in feed intake or a higher incidence of diarrhoea, although live weight and daily weight gain were reduced. Under the circumstances of this study and considering the effort related to the process, germination cannot be recommended as a method to improve the nutritive value and acceptance of faba beans for feeding of weaner pigs.

PCR-based verification of positive rapid diagnostic tests for intestinal protozoa infections with variable test band intensity

Stool-based rapid diagnostic tests (RDTs) for pathogenic intestinal protozoa (e.g. Cryptosporidium spp. and Giardia intestinalis) allow for prompt diagnosis and treatment in resource-constrained settings. Such RDTs can improve individual patient management and facilitate population-based screening programmes in areas without microbiological laboratories for confirmatory testing. However, RDTs are difficult to interpret in case of ‘trace’ results with faint test band intensities and little is known about whether such ambiguous results might indicate ‘true’ infections. In a longitudinal study conducted in poor neighbourhoods of Port Elizabeth, South Africa, a total of 1428 stool samples from two cohorts of schoolchildren were examined on the spot for Cryptosporidium spp. and G. intestinalis using an RDT (Crypto/Giardia DuoStrip; Coris BioConcept). Overall, 121 samples were positive for G. intestinalis and the RDT suggested presence of cryptosporidiosis in 22 samples. After a storage period of 9–10 months in cohort 1 and 2–3 months in cohort 2, samples were subjected to multiplex PCR (BD Max™ Enteric Parasite Panel, Becton Dickinson). Ninety-three percent (112/121) of RDT-positive samples for G. intestinalis were confirmed by PCR, with a correlation between RDT test band intensity and quantitative pathogen load present in the sample. For Cryptosporidium spp., all positive RDTs had faintly visible lines and these were negative on PCR. The performance of the BD Max™ PCR was nearly identical in both cohorts, despite the prolonged storage at disrupted cold chain conditions in cohort 1. The Crypto/Giardia DuoStrip warrants further validation in communities with a high incidence of diarrhoea.

A randomized controlled pilot study to evaluate the effect of an enteral formulation designed to improve gastrointestinal tolerance in the critically ill patient\u2014the SPIRIT trial

BackgroundDiarrhea is frequent in patients in intensive care units (ICU) and is associated with discomfort and complications and may increase the length of stay and nursing workload.MethodsThis was a prospective, double-blind, randomized, controlled single-center pilot study to assess the incidence and frequency of diarrhea and the respective effects of a modified enteral diet (intervention: Peptamen® AF, rich in proteins, medium chain triglycerides and fish oil) compared to a standard diet (control: Isosource® Energy) in 90 randomized adult patients (intervention, n = 46; control, n = 44) with an ICU stay ≥5 days and tube feeding ≥3 days. Tube feeding was initiated within 72 h of ICU admission and continued up to 10 days. The caloric goal was adjusted to needs by indirect calorimetry. Gastrointestinal function, nutritional intake, and nursing workload were recorded. Follow-up was until 28 days after randomization.ResultsMedian age was 63.3 (interquartile range (IQR) 51.0–73.2) years and Simplified Acute Physiology Score (SAPS) II was 61.0 (IQR 47.8–74). Time to reach caloric goal (intervention: 2.2 (0.8–3.7) days (median, IQR); control: 2.0 (1.3–2.7) days; p = 0.16), length of time on study nutrition (intervention: 5.0 (3.6–6.4) days; control: 7.0 (5.3–8.7) days; p = 0.26), and calorie intake (intervention: 18.0 (12.5–20.9) kcal/kg/day; control 19.7 (17.3–23.1) kcal/kg/day; p = 0.08) did not differ between groups, with a higher protein intake for Peptamen® group (1.13 (0.78–1.31) g/kg/day vs 0.80 (0.70–0.94); p < 0.001). No difference in diarrhea incidence (intervention group: 29 (64%); control group: 31 (70%); p = 0.652), use of fecal collectors (23 (51%) vs. 24 (55%); p = 0.83), or diarrhea-free days (161 (64%) vs 196 (68%); p = 0.65) was found. Nursing workload and cost for diarrhea care were not different between the groups. In a post-hoc analysis, adjusted for treatment group, age, sex, and SAPS II score, diarrhea was associated with length of mechanical ventilation (9.5 (6.0–13.1) vs. 3.9 (3.2–4.6) days; p = 0.006) and length of ICU stay (11.0 (8.9–13.1) vs. 5.0 (3.8–6.2) days; p = 0.001).ConclusionsIn this pilot study, we found a high incidence of diarrhea, which was not attenuated by Peptamen® AF. Patients with diarrhea stayed longer in the ICU.Trial registrationClinicalTrials.gov identifier, NCT01581957. Registered on 18 April 2012.

Influence of ad Libitum Feeding of Piglets With Bacillus Subtilis Fermented Liquid Feed on Gut Flora, Luminal Contents and Health

Some scholars caution that long-term ad libitum feeding with probiotic fermented food poses potential health risks to baby animals. We conducted a feeding experiment to investigate the influence of ad libitum feeding of pre-and post-weaned piglets with a Bacillus subtilis fermented diet on the gut microbiome, gut metabolomic profiles, bile acid metabolism, proinflammatory cytokines and faecal consistency. Compared with piglets fed a Bacillus subtilis-supplemented pellet diet, piglets fed the Bacillus subtilis fermented liquid diet had lower intestinal bacterial diversity (P > 0.05), higher intestinal fungal diversity (P > 0.05), more Firmicutes (P > 0.05), fewer Bacteroidetes, Actinobacteria and Proteobacteria (P > 0.05), higher concentrations of 3-hydroxypropionic acid (P < 0.05), orotic acid (P < 0.05), interleukin-6 (P < 0.01), lactic acid (P < 0.01), deoxycholic acid (P > 0.05) and lithocholic acid (P < 0.01) and a higher incidence of diarrhoea (P > 0.05). The data show that ad libitum feeding of piglets with a Bacillus subtilis fermented liquid diet during the suckling and early post-weaning periods promotes the growth of lactic acid bacteria, bile salt hydrolase-active bacteria and 7a-dehydroxylase-active bacteria in the intestinal lumen; disturbs the normal production of lactic acid, orotic acid and unconjugated bile acids; and increases circulating interleukin-6 levels and diarrhoea incidence.

Administration of non-pathogenic isolates of Escherichia coli and Clostridium perfringens type A to piglets in a herd affected with a high incidence of neonatal diarrhoea

A bacterial cocktail of living strains of Clostridium perfringens type A (CPA) without β2-toxin gene and non-pathogenic Escherichia coli was administered orally to newborn piglets before first colostrum intake and on 2 consecutive days on a farm with a high incidence of diarrhoea and antibiotic treatment in suckling piglets associated with E. coli and CPA. This clinical field study was driven by the hypothetic principle of competitive exclusion of pathogenic bacteria due to prior colonization of the gut mucosal surface by non-pathogenic strains of the same bacterial species with the aim of preventing disease. Although CPA strains used in this study did not produce toxins in vitro, their lack of pathogenicity cannot be conclusively confirmed. The health status of the herd was impaired by a high incidence of postpartum dysgalactia syndrome in sows (70%) and a high incidence of neonatal diarrhoea caused by enterotoxigenic E. coli and CPA during the study. No obvious adverse effect of the bacterial treatment occurred. On average, more piglets were weaned in litters treated (P=0.009). Visual pathological alterations in the small intestinal wall were more frequent in dead piglets of the control group (P=0.004) and necrotizing enteritis was only found in that group. A higher average daily weight gain of piglets in the control group (P<0.001) may be due to an increased milk uptake due to less competition in the smaller litters. The bacterial cocktail was tested under field conditions for its potential to stabilize gut health status in suckling piglets before disease development due to colibacillosis and clostridial infections; however, the gut flora stabilizing effect of the bacterial cocktail was not clearly discernible in this study. Further basic research is needed to confirm the positive effects of the bacterial treatment used and to identify additional potential bacterial candidates for competitive exclusion.

Effects of dietary peas mixed with linseed (3:1) on the growth performance, enteritis and certain serum parameter in weaned piglets

The objective of this work was to investigate the influence of dietary peas: linseed mixture (3:1) on the performance and certain serum biochemical parameters of weaned piglets. The faecal bacteriological and fungal composition and diarrhoea incidence was done as well. A total of 20 weaned piglets, 28 ± 3 days of age, were assigned randomly to 2 groups: control diet (C diet) with a classical diet (corn and soybean meal) and peas: linseed diet (PL diet, 3:1). The lipid and protein profile were determined by Analyser BS - 130. The cortisol serum concentration was determined with an Immulite 2000 (Siemens). The serum lipase concentration was determined by the spectropho - tometer method. The number of microorganisms from the faeces samples was determined by counting the colonies obtained on selected media for each particular microorganism. The dietary additismogisaac@gmail.comon of peas: linseed mixture did not influence the performance (P>0.05). The serum markers: cholesterol, triglycerides, total protein and their fraction did not differ significantly between treatments. Except the protein, which was slightly under the recommended limit, the other markers were within the physiological limits. The dietary fat content was similar. Serum lipase level in weaned piglets decreased insignific antly by dietary incorporation of pV10.5937/FFR1702173Heas: linseed (<9.06% in PL diet compared to C diet). The lower level of serum lipase in PL diet was reflected in a higher level of triglyceride (>1.10 times) and cholesterol (>1.06 times). The cortisol level was reduced by 94% by peas: linseed addition. The vegetable protein source did not have a significant influence on the bacteria of the faeces. After 2 weeks from weaning, the bacteria count was slowly higher in PL diet compared to C diet, as shown by a higher incidence of diarrhoea. We can conclude that peas and linseed are valuable vegetable sources for weaning piglets, their combination delivering an opportunity to have an optimal diet.

Short communication: Promotion of glucagon-like peptide-2 secretion in dairy calves with a bioactive extract from Olea europaea

Diarrhea episodes in dairy calves involve profound alterations in the mechanism controlling gut barrier function that ultimately compromise intestinal permeability to macromolecules, including pathogenic bacteria. Intestinal dysfunction models suggest that a key element of intestinal adaptation during the neonatal phase is the nutrient-induced secretion of glucagon-like peptide (GLP)-2 and associated effects on mucosal cell proliferation, barrier function, and inflammatory response. Bioactive molecules found in Olea europaea have been shown to induce the release of regulatory peptides from model enteroendocrine cells. The ability to enhance GLP-2 secretion via the feeding of putative GLP-2 secretagogues is untested in newborn calves. The objectives of this study were to determine whether feeding a bioactive extract from Olea europaea (OBE) mixed in the milk replacer (1) can stimulate GLP-2 secretion beyond the response elicited by enteral nutrients and, thereby, (2) improve intestinal permeability and animal growth as well as (3) reduce the incidence of diarrhea in preweaning dairy calves. Holstein heifer calves (n = 60) were purchased, transported to the research facility, and blocked by body weight and total serum protein and assigned to 1 of 3 treatments. Treatments were control (CON), standard milk replacer (MR) and ad libitum starter; CON plus OBE added into MR at 30 mg/kg of body weight (OBE30); and CON plus OBE added into MR at 60 mg/kg of body weight (OBE60). The concentration of GLP-2 was measured at the end of wk 2. Intestinal permeability was measured at the onset of the study and the end of wk 2 and 6, with lactulose and d-mannitol as markers. Treatments did not affect calf growth and starter intake. Compared with CON, administration of OBE60 increased the nutrient-induced response in GLP-2 by about 1 fold and reduced MR intake during the second week of study. Throughout the study, however, all calves had compromised intestinal permeability and a high incidence of diarrhea. The GLP-2 response elicited by OBE60 did not improve intestinal permeability (lactulose-to-d-mannitol ratio) and incidence of diarrhea over the course of the preweaning period. The response in GLP-2 secretion to the administration of OBE reported herein warrants further research efforts to investigate the possibility of improving intestinal integrity through GLP-2 secretion in newborn calves.

Covering the Cover

Covering the Cover

Impact of adherence to antiemetic guidelines on the incidence of chemotherapy-induced nausea and vomiting and quality of life.

Background International guidelines are tools enabling physicians to incorporate the latest evidence based clinical information into practice. Objective This study aimed to evaluate the impact of antiemetic guidelines adherence on the incidence of chemotherapy-induced nausea and vomiting (CINV) and patient quality of life. Setting Marmara University Pendik Training and Research Hospital chemotherapy unit, Istanbul, Turkey. Method The study included 100 chemotherapy naive patients. Antiemetic prescribing patterns and their consistency with MASCC/ESMO 2014 guidelines were assessed. Patients recorded incidences of vomiting in a daily dairy and described their nausea using a 7-item Likert Scale. The incidence of CINV was recorded over five days. To assess the patient's quality of life, a modified Turkish version of the Functional Living Index-Emesis (FLIE) questionnaire was administered before and after receiving chemotherapy. A questionnaire on the existence and severity of side effects was developed and administered. Main outcome measures Incidence of side effects on CINV and quality of life according to the FLIE. Results The primary outcome revealed differences in complete control (no emetic episodes, rescue therapy or nausea), FLIE scores and side effects. Guidelines consistency was observed more with acute (A) than with delayed (D) prevention of CINV, with significant differences in complete control between the guideline adherent group (GAG) and the guideline nonadherent group (GNG). Significant differences in the FLIE score were noticed between GAG(D) and GNG(D), and GNG(D) had a higher incidence of diarrhoea, headache, swallowing difficulties and dark-coloured stool. Conclusion Consistency with guidelines resulted in significant reduction in the incidence of both cute and delayed CINV and other side effects, and with improvement of the patient quality of life.

Severe weight loss during preoperative chemoradiotherapy compromises survival outcome for patients with locally advanced rectal cancer.

PurposeIn addition to tumor factors, poor nutritional status before and during anti-tumor treatment might compromise prognosis in several types of cancer. This study was done to determine the impact of weight loss during preoperative chemoradiotherapy (CRT) on the survival outcome of patients with locally advanced rectal cancer (LARC).MethodsThe retrospective study examined consecutive patients with LARC who underwent preoperative CRT followed by radical resection in a single institute, between 2003 and 2013. Correlation of proportional body mass index (BMI) change after preoperative CRT and patient’s demographics, tumor characteristics, treatment parameters, CRT-related toxicity, disease-free survival (DFS) and overall survival (OS) were investigated.ResultsA total of 364 patients were enrolled, and BMI loss was found in 243 patients (66.2 %) after preoperative CRT. Severe weight loss (SWL) was defined as BMI loss ≥7 %. Thirty-nine (10.7 %) cases were enrolled in SWL cohort and found to have higher incidence of diarrhea (P = 0.033), renal disorder (P = 0.033) and grade 3–4 radiation proctitis (P = 0.041). Although no significant difference was found in 3-year DFS, patients in SWL cohort showed significantly worse 3-year OS rate (71.8 vs 88.0 %, P = 0.030) than the others. In univariate analysis, BMI loss ≥7 %, completed dose of preoperative chemotherapy, pathologic T and N stages were correlated with OS (all P < 0.05). In multivariable analysis, BMI loss ≥7 % (HR 1.984; 95 % CI 1.061–3.709; P = 0.032) remained the independent prognostic factor for OS.ConclusionsOur results demonstrate that SWL during preoperative CRT indeed compromises survival outcome in patients with LARC. Routine nutritional monitoring and nutritional support during preoperative CRT are suggested as the integral part of the multidisciplinary approach for these patients.

Feeding practices among the infants presenting with acute diarrhea

Introduction: To study various feeding practices in children who present with acute watery diarrhea. The objective of the study was not only to study the feeding patterns but also draw an association between different feeding patterns and acute diarrheal episodes. Setting: Outdoor and indoor unit of Department of Paediatrics Jinnah Hospital affiliated with Allama Iqbal Medical College Lahore. Subject: Two hundred and fifty patients with acute watery diarrhea of less then 14 days between the ages of 1 month to 1 year were included in the study. Methods: It was a case control cross sectional study. The data related to 250 patients was collected. The required information was obtained from mother/ attendant of the infant in the questionnaire. All the questionnaire were filled by the doctors. Results: The majority of the infants with acute diarrhea were between 4 months to 1 year 195 (78%). Forty two (17%) were exclusively breastfed while 78 (31 %) exclusively bottle-fed. Fifty five (22%) had both breast feeding as well as bottle feeding. A large number of mothers 112 (44.8%) gave the reason of insufficient milk for the baby. Conclusion: Majority of the infants with acute diarrhea episodes were between 8 and 12 months when either breast milk is being replaced by bottle milk or improper weaning practices are being used. A large number of infants with acute diarrhea were either mixed fed or bottle fed. Because of increased mixed and bottle feeding there is high incidence of diarrhea in our community.

Assessing the tolerance of weanling pigs to a model feed flavour in the diet

A tolerance trial was carried out to evaluate the safety of feeding multifold doses of a model flavour containing a mixture of 20 chemically defined flavouring compounds to crossbred weanling piglets (Duroc male×Landrace/Large White female). Animals were weaned at 28 days and assigned to one of five treatments: a control (no flavour) or diets containing the model flavour at levels of 1×, 3×, 10× or 30× the typical commercial inclusion rate of 500mg/kg feed. A pre-starter diet was fed to piglets from 28 to 42 days of age and a starter diet from 42 to 70 days of age. Parameters measured included average daily gain (ADG), average daily feed intake (ADFI), feed conversion ratio FCR), haematology, serum biochemistry, general health and mortality. The model flavour was well tolerated by the piglets at all four dosage levels. No differences in ADFI or FCR were observed between treatment groups during the pre-starter/starter periods or for the whole trial. The ADG of piglets in receiving 3× the normal dosage was less (P<0.05) than that of the control animals, but not different from the other dosage groups. The group of piglets with the lower ADG had a higher incidence of diarrhoea than the other groups. Differences observed among treatments for the haematology and serum biochemistry parameters analysed were limited to piglets fed 3x the normal dosage. The extraction method developed to quantify the different compounds of the model flavour using routine GC/MS RTL is described. The importance of monitoring flavour content of the constituents present in the mixture and reducing losses due to volatility is highlighted. Results obtained from the trial demonstrate the feasibility of tolerance testing in target animal species using flavour mixtures.

Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): pooled subset analyses from two randomized trials

The irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases. The ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) studies randomized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib. EGFR mutation testing was performed centrally on archived tumor samples. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib. One hundred twenty-one patients with any EGFR mutation were enrolled; 101 had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median progression-free survival was 14.6 months [95% confidence interval (CI) 9.0-18.2] with dacomitinib and 9.6 months (95% CI 7.4-12.7) with erlotinib [unstratified hazard ratio (HR) 0.717 (95% CI 0.458-1.124), two-sided log-rank, P = 0.146]. The median survival was 26.6 months (95% CI 21.6-41.5) with dacomitinib versus 23.2 months (95% CI 16.0-31.8) with erlotinib [unstratified HR 0.737 (95% CI 0.431-1.259), two-sided log-rank, P = 0.265]. Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib. Dacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients. The subgroup with exon 19 deletion had favorable outcomes with dacomitinib. An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations (ARCHER 1050; NCT01774721). ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067).

Mother’s Knowledge, Attitude, Practice toward Safe Water Usage and Incidence of Diarrhea in Children at Baleendah Bandung

Background : Poor environmental conditions contribute to the high incidence of diarrhea, most of those caused by unsecure water and poor health knowledge. This study was conducted to evaluate the mother’s knowledge, attitude, and practice toward safe water usage in Baleendah, Bandung. Methods : A cross sectional descriptive study was conducted in Baleendah during September−October 2012, participated by 210 mothers with 12−59 months children, and using rapid survey method. This study used a questionnaire to measure the three domains, which consists of 8 questions of knowledge, 10 questions of attitudes, 16 questions of practice, and 7 questions of diarrhea. The collected data were analyzed and presented in table. Results : As much as 168 (80%) of mothers were in moderate knowledge status, 126 (60%) of mothers were in moderate attitude status. Practically, 127 (54.7%) of mothers used water from borehole/tube well. Most of the mothers (54.6%) use drinking water from refillable water store. Conclusions : Most mothers who participated have varied moderate knowledge and attitude status, and practice toward safe water usage. DOI : 10.15850/amj.v2n3.503

Cryptosporidium parvum infection and associated risk factors in dairy calves in western France

This study was conducted to determine the prevalence and risk factors for Cryptosporidium infection in calf neonates on dairy farms in Normandy.Fecal samples were randomly collected between July 2010 and September 2011 from 968 calves (7–21 days old) on 97 farms. Up to 10 calves were selected and sampled per farm, and feces examined for oocysts by microscopy. C. parvum oocyst shedding was scored semi-quantitatively (0–5). A questionnaire about calf-level care and management was completed, and mortality rates were obtained from the French national registration database (BDNI). Bivariable and multivariable analyses of potential risk factors for C. parvum oocyst shedding were conducted using generalized estimating equation (GEE) models (family=Binomial).Overall, 402 out of 968 calves (41.5%) were positive for oocysts, and 25.1% of animals had a shedding score >2. Seven of the 97 farms (7%) were negative for oocysts in all fecal samples. At the time of collection, 375 calves (39%) had diarrhea, and its prevalence strongly correlated with the score for C. parvum oocyst shedding (p<0.0001). The mortality rate at 90 days was significantly greater for calves with high combined scores of diarrhea and shedding. Factors associated with the shedding of C. parvum were the Normande breed (odds ratio=1.49; 95% confidence interval (CI): 0.93–2.37), dispensing of colostrum using a bucket (odds ratio=1.37; 95% CI: 1.00–1.89), treatment with halofuginone (odds ratio=0.46; 95% CI: 0.19–1.15) and feeding with fermented milk (odds ratio=0.32; 95% CI: 0.17–0.63).C. parvum is widespread among calves under 21 days old in dairy herds of western France. Shedding of C. parvum is associated with a high incidence of diarrhea and increased risk of mortality in young calves. This study identified some associated calf-level factors, although further investigations are necessary to determine appropriate measures that farmers and veterinary practitioners should take to reduce the prevalence of C. parvum.

Análise descritiva da diarreia em uma coorte de bezerras criadas em sistema de casinhas até cem dias de idade, Município de Piraí, Estado do Rio de Janeiro, Brasil

This study aimed to describe the diarrhea and parasites infection, evaluate the occurrence of failure of passive immunity transference and Escherichia coli EIEC/EPEC in heifer calves in calves from birth to one hundred days old, reared in individual crates under paddock. The feces collected weekly during the period September 2009 to June 2011 were examined by flotation in saturated sugar and centrifugal sedimentation in formalin-ether. The coagulation test by 10% glutaraldehyde was used to verify the transfer of passive immunity. The bacterial identification was performed from isolates in specific media. One hundred and eighteen heifers were followed, totaling 1457 fecal samples. The incidence rates of diarrhea and infection by Cryptosporidium, G. intestinalis, Eimeria and helminths were respectively 25.7, 13.2, 16.6, 26.9 and 16.7 new cases per 100 calves week. The average age of calves that had diarrhea was 54.2 ± 26.6, when they eliminated Cryptosporidium oocysts was 52.6 ± 26.1, cysts of G. intestinalis 40.1 ± 20 oocysts of Eimeria 49.5 ± 21.8 and Strongylida type eggs 64.9 ± 22.3 days. In none sample the intensity of infection by Cryptosporidium and Giardia was high. Samples of 62 calves were submited to bacteriological analysis and no sample was characterized as E. coli EPEC/EIEC. 69.6% of the calves, the amount of immunoglobulins was satisfactory. Despite the high incidence of diarrhea, mortality was low, due to low virulence of bioagents and low intensities of infection, as well as the system administration of colostrum and adopted creating the property. The similarity between the average age of calves with diarrhea and those eliminated Cryptosporidium spp. probably indicates that this bioagent, among those surveyed, is primarily responsible for diarrheal observed frames.