Protection of chickens vaccinated with combinations of commercial live infectious bronchitis vaccines containing Massachusetts, Dutch and QX-like serotypes against challenge with virulent infectious bronchitis viruses 793B and IS/1494/06 Israel variant 2.

Infectious bronchitis virus (IBV) is a coronavirus which affects chickens of all ages. IBV mainly causes respiratory disease but can also result in reduced weight gain, reduced egg production, increased frequency of abnormal eggs and increased rates of mortality. Vaccination is the most important way to control the disease. Nevertheless, novel strains of infectious bronchitis (IB) continue to emerge in the field. In order to respond promptly, combinations of existing IB vaccines are frequently tested to see whether they can provide cross-protection. The efficacy of a combination of vaccines based on Massachusetts, Dutch and QX-like IB strains against emerging IB Israel variant 2 and IB 793B strains was assessed by means of four challenge studies. At least 80% of the birds vaccinated with IB H120 (Mass type) combined with IB D274 (Dutch type) followed by a QX-like IB vaccine booster or vaccinated with a combination of IB H120, IB D274 and QX-like IB were protected against a challenge with IB 793B. In addition, IB 1263 (Mass type) boosted by QX-like IB showed an 85% protection following challenge with IB 793B. A combination of IB H120 and IB D274 boosted by QX-like IB vaccine conferred 70% protection whilst H120 and IB D274 combination on its own showed 61.1% protection against Israel variant 2 challenge. IB 1263 boosted by a QX-like IB vaccine showed 50% protection against IB Israel variant 2. Therefore, it can be concluded that a combination of the IB H120, IB D274 and QX-like IB confers broad protection against different non-related virulent IB strains.

The impact of practice guidelines in the management of Barrett esophagus: a national prospective cohort study of physicians.

BACKGROUND: Surveillance of patients with Barrett esophagus (BE) is recommended to detect dysplasia and early cancer. In 1998, practice guidelines for the surveillance of patients with BE were developed under the auspices of the American College of Gastroenterology (ACG). Our objective is to assess physicians' awareness of agreement with and adherence to these guidelines. METHODS: A national prospective cohort study of practicing gastroenterologists who completed a self-administered questionnaire containing case studies prior to the release of the guidelines and another survey 18 months later. Analysis of adherence to the guidelines was done using the McNemar chi(2) test. RESULTS: Of the 154 gastroenterologists (66%) who responded to the follow-up survey, more than half (55%) were aware of the guidelines, and members of the ACG were more likely to know of their existence than nonmembers (61% vs 38%; P =.01). Overall, about 27% of physicians reported practicing in accordance with the guidelines at baseline; adherence increased modestly to 38% in the 18-month follow-up (P =.04) and was inversely related to fee-for-service reimbursement. Awareness was not associated with an increased likelihood of adherence, but agreement with the guidelines was strongly correlated with adherence (P<.001). The most frequent reasons for disagreement were concerns about liability, cancer risk, and inadequate evidence. CONCLUSIONS: Awareness of the guidelines published by the ACG was low. Guideline awareness did not predict adherence. Improvement in guideline adherence will require steps beyond mere dissemination and promotion. Addressing disagreements about liability, disease risk, and scientific evidence as well as restructuring payment incentives may help achieve optimal practice.

Revised estimates of diagnostic test sensitivity and specificity in suspected biliary tract disease.

BACKGROUND: The purpose of this study was to estimate the sensitivity and specificity of diagnostic tests for gallstones and acute cholecystitis. METHODS: All English-language articles published from 1966 through 1992 about tests used in the diagnosis of biliary tract disease were identified through MEDLINE. From 1614 titles, 666 abstracts were examined and 322 articles were read to identify 61 articles with information about sensitivity and specificity. Application of exclusion criteria based on clinical and methodologic criteria left 30 articles for analysis. Cluster-sampling methods were adapted to obtain combined estimates of sensitivities and specificities. Adjustments were made to estimates that were biased because the gold standard was applied preferentially to patients with positive test results. RESULTS: Ultrasound has the best unadjusted sensitivity (0.97; 95% confidence interval, 0.95 to 0.99) and specificity (0.95; 95% confidence interval, 0.88 to 1.00) for evaluating patients with suspected gallstones. Adjusted values are 0.84 (0.76 to 0.92) and 0.99 (0.97 to 1.00), respectively. Adjusted and unadjusted results for oral cholecystogram were lower. Radionuclide scanning has the best sensitivity (0.97; 95% confidence interval, 0.96 to 0.98) and specificity (0.90; 95% confidence interval, 0.86 to 0.95) for evaluating patients with suspected acute cholecystitis; test performance is unaffected by delayed imaging. Unadjusted sensitivity and specificity of ultrasound in evaluating patients with suspected acute cholecystitis are 0.94 (0.92 to 0.96) and 0.78 (0.61 to 0.96); adjusted values are 0.88 (0.74 to 1.00) and 0.80 (0.62 to 0.98). CONCLUSIONS: Ultrasound is superior to oral cholecystogram for diagnosing cholelithiasis, and radionuclide scanning is the test of choice for acute cholecystitis. However, sensitivities and specificities are somewhat lower than commonly reported. We recommend estimates that are midway between the adjusted and unadjusted values.

Safety of probiotics and synbiotics in children under 18 years of age.

This study aimed to systematically evaluate safety of probiotics and synbiotics in children ageing 0-18 years. This study is the third and final part in a safety trilogy and an update is provided using the most recent available clinical data (2008-2013) by means of the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 74 clinical studies indicated that probiotic and/or synbiotic administration in children is safe with regard to the specific evaluated strains, dosages and duration. The population of children include healthy, immune compromised and obese subjects, as well as subjects with intestinal disorders, infections and inflammatory disorders. This study revealed no major safety concerns, as the adverse events (AEs) were unrelated, or not suspected to be related, to the probiotic or synbiotic product. In general the study products were well tolerated. Overall, AEs occurred more frequent in the control arm compared to children receiving probiotics and/or synbiotics. Furthermore, the results indicate inadequate reporting and classification of AEs in the majority of the studies. In addition, generalizability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes.

The administration of probiotics and synbiotics in immune compromised adults: is it safe?

This study aimed to systematically evaluate safety of probiotics and synbiotics in immune compromised adults (≥18 years). Safety was analysed using the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification, thereby providing an update on previous reports using the most recent available clinical data (2008-2013). Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 57 clinical studies indicates that probiotic and/or synbiotic administration in immune compromised adults is safe with regard to the current evaluated probiotic strains, dosages and duration. Individuals were considered immune compromised if HIV-infected, critically ill, underwent surgery or had an organ- or an autoimmune disease. There were no major safety concerns in the study, as none of the serious adverse events (AE)s were related, or suspected to be related, to the probiotic or synbiotic product and the study products were well tolerated. Overall, AEs occurred less frequent in immune compromised subjects receiving probiotics and/or synbiotics compared to the control group. In addition, the results demonstrated a flaw in precise reporting and classification of AE in most studies. Furthermore, generalisability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes. We argue that standardised reporting on adverse events (CTCAE) in 'food' studies should be obligatory, thereby improving reliability of data and re-enforcing the safety profile of probiotics.

Consequences of the delayed diagnosis of ataxia-telangiectasia.

OBJECTIVES: Ataxia-telangiectasia (AT) is a rare, autosomal recessive neurodegenerative disorder in which the diagnosis is obvious when ataxia and telangiectasia are both present. However, the diagnosis can be made upon the onset of ataxia and before the appearance of telangiectasia if confirmed by laboratory tests. Early diagnosis is important for genetic counseling, appropriate care, and avoidance of unnecessary tests. The purpose of this study is to identify factors responsible for delays in the diagnosis of AT. DESIGN: The records of all patients seen at the Ataxia-Telangiectasia Clinical Center from July 1, 1995 to April 1, 1997 were reviewed to determine age of onset of gait abnormality, recognition of telangiectasia, and diagnosis. RESULTS: In 48 patients with AT, who were the index cases in their respective families, the median age of diagnosis (78 months) occurred after the onset of gait abnormalities (15 months) and closely corresponded to the development of telangiectasia (72 months). In the majority of cases (34/48), telangiectasia appeared before the diagnosis was established. The most common misdiagnosis was cerebral palsy (29/48 cases). Twenty-one children (4 with AT) were born after the start of symptoms in the index case, but before the establishment of a diagnosis. CONCLUSIONS: The term AT, although a concise and memorable label for the disorder, is also a barrier to early diagnosis. We recommend the use of routine serum alpha-fetoprotein testing for all children with persistent ataxia.

Hepatitis B vaccination practices in hospital newborn nurseries before and after changes in vaccination recommendations.

BACKGROUND: Routine use of hepatitis B vaccine for low-risk newborns was suspended on July 7, 1999, because of concern about the potential risk of thimerosal, a mercury-containing vaccine preservative. Reinstatement of the birth dose was recommended when a thimerosal-free vaccine became available. OBJECTIVE: To explore changes in hepatitis B vaccination practices for newborns related to the revised recommendations for low-risk infants (in this study, the terms newborn and infant are used interchangeably). DESIGN: A telephone survey of a random sample of 1000 US hospitals. PARTICIPANTS: Nurse managers, nursery directors, and staff nurses of the newborn nurseries. MAIN OUTCOME MEASURES: Nursery vaccination practices before and after July 7, 1999, and the availability and use of thimerosal-free vaccine. RESULTS: Interviews were conducted with 773 (87%) of 886 eligible hospitals. Before July 7, 1999, 78% of the hospitals reported vaccination practices that were consistent with recommendations at that time, although only 47% vaccinated all low-risk infants at birth. After July 7, 1999, almost all hospitals discontinued vaccination of low-risk infants, in accordance with the recommendation change; however, there was a 6-fold increase in the number of hospitals that were not vaccinating all high-risk infants. After the introduction of thimerosal-free vaccine, only 39% of the hospitals reported vaccinating all low-risk infants. CONCLUSIONS: Most hospital nurseries altered their newborn hepatitis B vaccination practices consistent with changes in national recommendations. However, unintended consequences included the failure of some hospitals to continue vaccinating all high-risk infants and the delay in reintroducing vaccination for low-risk newborns after the introduction of a thimerosal-free vaccine. Assessments of the appropriateness of this country's response to the threat of thimerosal in vaccines should consider these findings.

Reasons for pediatrician nonadherence to asthma guidelines.

BACKGROUND: The 1997 National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines include recommendations on how to improve the quality of care for asthma. OBJECTIVE: To identify barriers to physician adherence to the NHLBI guidelines. DESIGN: Cross-sectional survey. PARTICIPANTS: A national random sample of 829 primary care pediatricians. MAIN OUTCOME MEASURES: Self-reported adherence to 4 components of the NHLBI guidelines (steroid prescription, instructing peak flow meter use, screening and counseling patients with asthma for smoking, and screening and counseling parents for smoking). We also collected information on physician demographics, practice characteristics, and possible barriers to adherence. We defined adherence as following a guideline component more than 90% of the time. RESULTS: The response rate was 55% (456/829). Most of the responding pediatricians were aware of the guidelines (88%) and reported having access to a copy of the guidelines (81%). Self-reported rates of adherence were between 39% and 53% for the guideline components. After controlling for demographics and other barriers, we found that nonadherence was associated with specific barriers for each guideline component: for corticosteroid prescription, lack of agreement (odds ratio [OR], 6.8; 95% confidence interval [CI], 3.2-14.4); for peak flow meter use, lack of self-efficacy (OR, 3.4; 95% CI, 1.9-6.1) and lack of outcome expectancy (OR, 4.7; 95% CI, 2.5-8.9); and for screening and counseling of patients and parents for smoking, lack of self-efficacy (OR, 3.8; 95% CI, 1.7-6.2 and OR, 2.8; 95% CI, 1.3-5.9, respectively). CONCLUSIONS: Although pediatricians in this sample were aware of the NHLBI guidelines, a variety of barriers precluded their successful use. To improve NHLBI guideline adherence, tailored interventions that address the barriers characteristic of a given guideline component need to be implemented.

Barriers pediatricians face when using asthma practice guidelines.

OBJECTIVE: To describe barriers to the successful use of the 1997 National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines. METHODS: We conducted 3 focus groups to understand barriers to the use of 4 recommendations within the NHLBI guidelines (prescription of inhaled corticosteroids, recommendation of daily peak flowmeter use, smoking cessation screening and counseling, and allergen exposure counseling). PARTICIPANTS: Twenty-one pediatricians and 1 nurse practitioner, who each followed an average of 47 patients with asthma, participated. Six participants (27%) had a faculty or adjunct appointment at a medical school. Nineteen (90%) of the 21 pediatricians were board certified. RESULTS: We identified 171 comments about barriers to adherence. Type of recommendation and physician year of graduation from medical school were related to which barrier was prominent. For corticosteroid prescription, senior physicians mentioned lack of agreement, whereas younger physicians described lack of confidence in dosing or recognizing contraindications. For peak flow-meter use, senior physicians emphasized lack of training. Only senior physicians described the inertia of previous practice as a barrier. All groups mentioned time limitations. CONCLUSIONS: Efforts to improve adherence to asthma guidelines should consider the range of barriers that pediatricians face, such as lack of awareness, familiarity, or agreement, and external barriers owing to environmental, guideline, or patient factors. In addition, this study documents barriers not previously considered, such as lack of self-efficacy, lack of outcome expectancy, and inertia of previous practice, that prevent adherence. Because type of recommendation and physician demographics are related to which barriers are prominent, interventions to improve NHLBI guideline adherence should be tailored to these factors.

Morphine-augmented hepatobiliary scintigraphy: a meta-analysis.

The aim of this study was to compare the sensitivity and specificity of morphine-augmented hepatobiliary scintigraphy (MA-HBS) with that of conventional hepatobiliary scintigraphy (C-HBS) for acute cholecystitis. The results of most MA-HBS studies cannot be compared with C-HBS estimates, since articles describing C-HBS often include non-candidates for MA-HBS. However, using meta-analytic techniques to combine data from eligible studies (4 for C-HBS and 5 for MA-HBS), the specificity of MA-HBS (0.84; 95% CI = 0.75-0.94) was significantly greater (P = 0.008) than that of C-HBS (0.68; 95% CI = 0.61-0.75); there were no differences in sensitivity (MA-HBS; 0.96, 95% CI = 0.92-0.99; C-HBS: 0.97, 95% CI = 0.97-0.99).

Suicidal traits in Marilyn Monroe's Fragments: an LIWC analysis.

BACKGROUND: Linguistic inquiry and word count (LIWC), a computerized method for text analysis, is often used to examine suicide writings in order to characterize the quantitative linguistic features of suicidal texts. AIMS: To analyze texts compiled in Marilyn Monroe's Fragments using LIWC, in order to explore the use of different linguistic categories in her narrative over the years. METHOD: Selected texts were grouped into four periods of similar word count and processed with LIWC. Spearman's rank correlation was used to assess changes in language use across the documents over time. The Kruskal-Wallis test was applied to compare means between periods and for each of the 80 LIWC output scores. RESULTS: Significant differences (p < .05) were found in 11 categories, the most relevant being a progressive decrease in the use of negative emotion words, a reduction in the use of long words in the third period, and an increase in the proportion of personal pronouns used as Monroe approached the time of her death. CONCLUSIONS: The consistently elevated usage of first-person personal singular pronouns and the consistently diminished usage of first-person personal plural pronouns are in line with previous studies linking this pattern with a low level of social integration, which has been related to suicide according to different theories.

Emergence and genetic evolution of HIV-1 variants with mutations conferring resistance to multiple reverse transcriptase and protease inhibitors.

The emergence of genotypic resistance in protease and reverse transcriptase (RT) gene regions was longitudinally evaluated in plasma samples from a group of 12 HIV-1-infected patients treated with different combination of antiretroviral therapies and selected on the basis of their clinical failure. Complex mutational patterns in the reverse transcriptase gene were observed. In particular, combinations of AZT (41L, 67N, 70R, 210W, and 219Q/E) and 3TC (184M) were seen in 10 patients. Two patients presented codon 151 multinucleoside analogue resistance (MNR). Additionally, seven patients harbored RT nonnucleoside analogue-related resistance substitutions (98G, 103N, and 181C). Multiple protease-selected mutations were found in each patient with an average of six substitutions per patient, with 10I/F/V, 63P, 71V, 82A/T, 84V, and 90M being the most prevalent substitutions. Overall, these results showed that for most patients virological failure was coupled with detectable genotypic resistance. Furthermore, most patients exhibited genotypic resistance to almost all available anti-HIV-1 drugs. The high viral loads found in most patients at the end of the study suggest that the replication of these multidrug resistant viruses are not severely compromised. Phylogenetic analysis of these pol sequences revealed that a specific HIV-1 genotype prone to develop multidrug resistance was not found.

Asymptomatic gallstones revisited. Is there a role for laparoscopic cholecystectomy?

OBJECTIVE: To compare the mortality effects of prophylactic laparoscopic cholecystectomy with that of expectant management in persons with asymptomatic gallstones. DESIGN: Decision analytic models of the two clinical strategies using input data from a review of the published medical literature pertaining to the epidemiology, natural history, and treatment outcomes related to gallstone disease. PATIENTS: Cohorts of men and women aged 30 and 50 years with asymptomatic gallstones. INTERVENTION: Prophylactic laparoscopic cholecystectomy performed at the time of diagnosis of asymptomatic gallstones or expectant management, defined as therapeutic intervention delayed until gallstone symptoms or complications spontaneously develop. MAIN OUTCOME MEASURES: Gallstone-related deaths and gallstone-related life-years lost for each age and gender cohort, by strategy. Models were subjected to rigorous sensitivity analysis to test the robustness of the results to changes in individual input variables. Outcomes were calculated with and without discounting nonfinancial benefits. RESULTS: The prophylactic laparoscopic cholecystectomy strategy led to fewer gallstone-related deaths than the expectant management strategy, but all of the deaths in the prophylactic laparoscopic cholecystectomy group occurred earlier in life. In cohorts older than age 30 years, the expectant management strategy resulted in fewer undiscounted gallstone life-years lost than the prophylactic laparoscopic cholecystectomy strategy. Discounting favored expectant management further because life-years lost were delayed compared with prophylactic surgery. Sensitivity analysis demonstrated the superiority of expectant management over a wide range of input assumptions. CONCLUSIONS: Prophylactic laparoscopic cholecystectomy should not be routinely recommended for individuals with asymptomatic gallstones.