Respiratory syncytial virus and other respiratory viral infections in older adults with moderate to severe influenza-like illness.

BACKGROUND: Few studies have prospectively assessed viral etiologies of acute respiratory infections in community-based elderly individuals. We assessed viral respiratory pathogens in individuals ≥65 years with influenza-like illness (ILI). METHODS: Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal/throat swabs from 556 episodes of moderate-to-severe ILI, defined as ILI with pneumonia, hospitalization, or maximum daily influenza symptom severity score (ISS) >2. Cases were selected from a randomized trial of an adjuvanted vs nonadjuvanted influenza vaccine conducted in elderly adults from 15 countries. RESULTS: Respiratory syncytial virus (RSV) was detected in 7.4% (41/556) moderate-to-severe ILI episodes in elderly adults. Most (39/41) were single infections. There was a significant association between country and RSV detection (P = .004). RSV prevalence was 7.1% (2/28) in ILI with pneumonia, 12.5% (8/64) in ILI with hospitalization, and 6.7% (32/480) in ILI with maximum ISS > 2. Any virus was detected in 320/556 (57.6%) ILI episodes: influenza A (104/556, 18.7%), rhinovirus/enterovirus (82/556, 14.7%), coronavirus and human metapneumovirus (each 32/556, 5.6%). CONCLUSIONS: This first global study providing data on RSV disease in ≥65 year-olds confirms that RSV is an important respiratory pathogen in the elderly. Preventative measures such as vaccination could decrease severe respiratory illnesses and complications in the elderly.

CONTOUR Australia: Condition of Submental Fullness and Treatment Outcomes with Belkyra Registry.

Submental fat (SMF) contributes to an aged or overweight appearance that may negatively impact an individual's psychological well-being. Deoxycholic acid (ATX-101) is an injectable formulation of deoxycholic acid approved to treat SMF. The Condition of Submental Fullness and Treatment Outcomes Registry (CONTOUR) Australia study was designed to understand treatment patterns and outcomes with ATX-101 in Australia. Methods: CONTOUR Australia was a phase 4, prospective, observational, multicenter registry that enrolled adults considering treatment for SMF reduction. Results: The registry enrolled 86 patients from six sites. Significant changes from baseline through the end of treatment indicated improvement in mild to moderate fullness associated with SMF on the Clinician-Reported SMF Rating Scale and the Patient-Reported SMF Rating Scale, improvement in SMF-associated psychological impact after treatment on the Patient-Reported SMF Impact Scale, no overall worsening in skin laxity based on Submental Skin Laxity Grade, and increased patient satisfaction with the face/chin on the Subject Self-Rating Scale after receiving treatment. Adverse events were all mild and mostly related to the injection site (ie, bruising and swelling). Conclusion: CONTOUR Australia observed clinically meaningful and significant outcomes and further supports ATX-101 as a well-tolerated and effective treatment for SMF reduction.

Silent spread of H5N1 in vaccinated poultry.

International debate on the merits of vaccinating poultry against the H5N1 influenza A virus has raised concerns about the possibility of an increased risk of between-flock transmission before outbreaks are detected. Here we show that this 'silent spread' can occur because of incomplete protection at the flock level, even if a vaccine is effective in individual birds. The use of unvaccinated sentinels can mitigate, although not completely eliminate, the problem.

Evaluation of swallowing by Sydney Swallow Questionnaire (SSQ) in oral and oropharyngeal cancer patients treated with primary surgery.

This work aimed at evaluating patients' swallowing functions by a newly validated swallow-specific questionnaire, the Sydney Swallow Questionnaire (SSQ), in a cohort of oral and oropharyngeal cancer patients. Mean/median SSQ scores were calculated and compared with study variables using the Mann-Whitney U test and Kruskal-Wallis test. The mean composite SSQ scores (SD) for the base of tongue, oral tongue, and tonsillar cancer patients were 663.8 (382.8), 456.2 (407.6), and 283.0 (243.1), respectively (p = 0.005); for advanced vs. early T stage disease they were 918.1 (319.5) vs. 344.8 (292.1) (p ≤ 0.001); for patients <60 years vs. ≥60 years they were 549.3 (415.1) vs. 314.0 (247.3) (p = 0.02); and for patients with reconstruction vs. without reconstruction they were 676.5 (410.5) vs. 331.9 (286.5) (p = 0.002). SSQ is a useful tool for evaluation of swallowing in head and neck cancer patients. Site of cancer, T stage, patient's age, and reconstruction directly affect post-treatment swallow outcome.

An exploratory study of the influence of clinico-demographic variables on swallowing and swallowing-related quality of life in a cohort of oral and oropharyngeal cancer patients treated with primary surgery.

There are insufficient data on swallowing and the consequences of its dysfunction in patients with cancers of the oral cavity (OC) and oropharynx (OP) that are treated with primary surgery. The study attempts to explore the effect of important clinico-demographic variables on post-treatment swallowing and related quality of life (QOL) in post-surgical OC and OP cancer patients. Sixty-two consecutive OC and OP cancer patients completed the MD Anderson Dysphagia Inventory (MDADI) questionnaire. Mean scores were computed. Comparison of scores based on mean ranks were performed using Mann-Whitney U test or Kruskal-Wallis test. Level of significance was set at P ≤ 0.02. Adjustments were made for multiple comparisons. Significantly worse mean (SD) QOL scores were observed in late T-stage (T3/T4) versus early T-stage (T1/T2) patients for global domain, physical domain, functional domain and emotional domains [44.4 (21.9) vs. 78.7 (22.7) (P < 0.001); 50.0 (9.4) vs. 75.9 (16.3), (P < 0.0001); 57.8 (20.6) vs. 84.1 (16.7), (P < 0.001) and 55.2 (18.0) vs. 78.5 (16.3), (P < 0.001)], respectively. Patients undergoing reconstruction versus without reconstruction had worse QOL scores; 58.8 (26.9) versus 79.5 (22.8), (P < 0.01); 61.2 (15.1) versus 76.4 (17.5), (P = 0.002); 65.4 (20.5) versus 86.3 (15.9), (P < 0.0001) and 63.3 (18.8) versus 79.8 (16.3), (P < 0.01), respectively, for global, physical, functional and emotional domains. Advanced T-stage, reconstruction, younger age and base of tongue tumours have a negative impact on post-treatment swallow function and related QOL in these patients.

Evaluation of factors affecting post-treatment quality of life in oral and oropharyngeal cancer patients primarily treated with curative surgery: an exploratory study.

The aim was to explore the impact of important clinico-demographic factors on the post-treatment quality of life (QOL) in surgically treated oral and oropharyngeal cancer patients. 63 consecutive follow-up oral and oropharyngeal cancer patients treated primarily with surgery were recruited. 55 patients sent the completed questionnaires and finally included in this study. QOL and important sub-domains of the QOL were assessed. Mean QOL scores (SD) were computed, level of significance was set at P < 0.05. The mean composite QOL score and standard deviation (SD) for oral and oropharyngeal cancer patients were 76.6 (15.2) and 73.4 (13.9), respectively. Patients with higher T-stage (T3 and T4) and higher overall-stage (III and IV) had lower mean QOL scores as against early T (T1 and T2) and overall early-stage (I and II); mean scores (SD) 64.3 (13.6) and 72.3 (13.8), and 76.6 (13.6) and 81.7 (14.1), respectively. Younger patients had lower mean scores (SD) than older patients; mean QOL scores (SD) 69.7 (14.0) and 79.6 (SD), respectively. Patients with reconstruction had lower mean QOL scores as compared to those without reconstruction; mean scores (SD) 67.6 (16.0) and 77.4 (12.5), respectively. In conclusion, tumor-stage, overall-stage, age of patients, and reconstruction had a significant direct effect on the post-treatment QOL of oral and oropharyngeal cancer patients.

Real-World Safety And Effectiveness Of OnabotulinumtoxinA Treatment Of Crow's Feet Lines And Glabellar Lines: Results Of A Korean Postmarketing Surveillance Study.

PURPOSE: OnabotulinumtoxinA is approved in the Republic of Korea for the treatment of moderate-to-severe crow's feet lines (CFL) and glabellar lines (GL), separately or in combination. We assessed safety and effectiveness of onabotulinumtoxinA in real-world clinical practice. PATIENT AND METHODS: This 4-year postmarketing surveillance study was conducted in the Republic of Korea in subjects with moderate-to-severe CFL. Subjects aged 18 to 75 years received onabotulinumtoxinA injections for CFL alone or in combination with GL. Safety assessments included adverse events (AEs), serious AEs (SAEs), and unexpected AEs (not noted in Korean prescribing information). Investigators assessed effectiveness via change from baseline in CFL. RESULTS: The full analysis set comprised 695 subjects; 667 were in the safety set and 376 in the effectiveness set. In the safety set, mean ± SD age was 40.9±13.0 years; most subjects (87.3%) were female. More subjects were treated for CFL (69.9%) than CFL and GL simultaneously (30.1%). Eleven subjects experienced 14 AEs; 12 were mild in severity and 11 resolved without sequelae. Two cases of injection site pain in 2 subjects each were deemed possibly related to onabotulinumtoxinA. One unexpected SAE (acute renal failure) occurred in 1 subject (0.15%). All unexpected AEs (n=4) were mild and considered unrelated to treatment. Overall change from baseline showed CFL was improved in 375 subjects (99.7%) and unchanged in 1 subject (0.3%). CONCLUSION: OnabotulinumtoxinA was well tolerated and effective for treatment of CFL with or without GL in a real-world Korean population. No new safety concerns were identified.

Detection of mortality clusters associated with highly pathogenic avian influenza in poultry: a theoretical analysis.

Rapid detection of infectious disease outbreaks is often crucial for their effective control. One example is highly pathogenic avian influenza (HPAI) such as H5N1 in commercial poultry flocks. There are no quantitative data, however, on how quickly the effects of HPAI infection in poultry flocks can be detected. Here, we study, using an individual-based mathematical model, time to detection in chicken flocks. Detection is triggered when mortality, food or water intake or egg production in layers pass recommended thresholds suggested from the experience of past HPAI outbreaks. We suggest a new threshold for caged flocks--the cage mortality detection threshold--as a more sensitive threshold than current ones. Time to detection is shown to depend nonlinearly on R0 and is particularly sensitive for R0<10. It also depends logarithmically on flock size and number of birds per cage. We also examine how many false alarms occur in uninfected flocks when we vary detection thresholds owing to background mortality. The false alarm rate is shown to be sensitive to detection thresholds, dependent on flock size and background mortality and independent of the length of the production cycle. We suggest that current detection thresholds appear sufficient to rapidly detect the effects of a high R0 HPAI strain such as H7N7 over a wide range of flock sizes. Time to detection of the effects of a low R0 HPAI strain such as H5N1 can be significantly improved, particularly for large flocks, by lowering detection thresholds, and this can be accomplished without causing excessive false alarms in uninfected flocks. The results are discussed in terms of optimizing the design of disease surveillance programmes in general.

Quantification of Peyer's patches in Cheviot sheep for future scrapie pathogenesis studies.

Peyer's patches (PPs) are the most probable sites of intestinal uptake of the transmissible spongiform encephalopathy (TSE) agent. The amount of PP tissue varies considerably between different age groups of individuals, and whether this variation is related to susceptibility to TSE infection raises an intriguing possibility. The purpose of this study was to determine the surface area of PP tissue and the number of associated lymphoid follicles in different age groups of Neuropathogenesis Unit (NPU) Cheviot sheep. Terminal ilea were obtained from 33 sheep of different ages. Samples of ileal tissue were collected for immunocytochemistry and immunolabelled for prion protein (PrP). Specimens were then fixed in acetic acid, stained with methylene blue and transilluminated. Image analysis software was used to calculate the area of intestinal and PP tissue. The number of associated lymphoid follicles was determined using a dissecting microscope. Results showed a marked fall in surface area of PP tissue and lymphoid follicle density around puberty (about 8-9 months of age in NPU Cheviot sheep) and both measures remained low throughout adulthood. Using the Spearman's rank correlation coefficient, r(s), these two measures were found to be closely correlated (r(s)=0.899, n=33, P<0.0001). There was also a significant (negative) correlation between age and the two respective measures (surface area of PP tissue versus age, r(s)=-0.879 (n=33, P<0.0001); lymphoid follicle density versus age r(s)=-0.943 (n=33, P<0.0001). Immunolabelling for PrP was observed primarily in the light zone of lymphoid follicles. Results obtained from this study are useful for future oral pathogenesis studies of the NPU Cheviot flock. They may also offer a possible biological explanation for the apparent age-susceptibility relationship observed in natural cases of TSEs and might help to explain the young age-distribution of cases.

Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies.

BACKGROUND: Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE) and variant CJD (vCJD), and the development of lymphoid tissue in the gut. METHODS: Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies) for sheep, cattle and humans, we calculated the Spearman's rank correlation coefficient, rs, between available measures of Peyer's patch (PP) development and the estimated risk of infection for an individual of the corresponding age. RESULTS: There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, rs = 0.913 (n = 19, P < 0.001), and lymphoid follicle density vs risk of infection, rs = 0.933 (n = 19, P < 0.001); for cattle, weight of PP tissue vs risk of infection, rs = 0.693 (n = 94, P < 0.001); and for humans, number of PPs vs risk of infection, rs = 0.384 (n = 46, P = 0.008). In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: rs = 0.360 (n = 46, P = 0.014). CONCLUSION: Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development) and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species.

Acoustic parameters of speech: Lack of correlation with perceptual and questionnaire-based speech evaluation in patients with oral and oropharyngeal cancer treated with primary surgery.

BACKGROUND: Acoustic evaluation of speech is the least explored method of speech evaluation in patients with oral cavity and oropharyngeal cancer. The purpose of this study was to explore acoustic parameters of speech and their correlation with questionnaire evaluation and perceptual evaluation in patients with oral cavity and oropharyngeal cancer. METHODS: One hundred seventeen subjects (65 consecutive patients with oral cavity and oropharyngeal cancer and 52 controls) participated in this study. Formant frequencies (by Linear Predictive Coding), Speech Handicap Index, and London Speech Evaluation scale were used for acoustic evaluation, questionnaire evaluation, and perceptual evaluation, respectively. RESULTS: Men showed significant elevation in second formant (F2) values for patients with oral cavity cancer and those who underwent surgery alone. Female patients with early T classification cancers and those who underwent surgery and chemoradiation showed significant reduction in the mean F2 values. Importantly, however, acoustic evaluation parameters did not correlate with either perceptual evaluation or questionnaire evaluation parameters, although there was moderate correlation between questionnaire evaluation and perceptual evaluation speech parameters. CONCLUSION: Acoustic evaluation modalities have no clear role in the management of patients with oral cavity and oropharyngeal cancer.

Dose-escalated intensity-modulated radiotherapy is feasible and may improve locoregional control and laryngeal preservation in laryngo-hypopharyngeal cancers.

PURPOSE: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). METHODS AND MATERIALS: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. RESULTS: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. CONCLUSIONS: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III study.

Evaluation of speech outcomes using English version of the Speech Handicap Index in a cohort of head and neck cancer patients.

The aim of this study was to explore post-treatment speech impairments using English version of Speech Handicap Index (SHI) (first speech-specific questionnaire) in a cohort of oral cavity (OC) and oropharyngeal (OP) cancer patients. Sixty-three consecutive OC and OP cancer patients in follow-up participated in this study. Descriptive analyses have been presented as percentages, while Mann-Whitney U-test and Kruskall-Wallis test have been used for the quantitative variables. Statistical Package for Social Science-15 statistical software (SPSS Inc., Chicago, IL) was used for the statistical analyses. Over a third (36.1%) of patients reported their speech as either average or bad. Speech intelligibility and articulation were the main speech concerns for 58.8% and 52.9% OC and 31.6% and 34.2% OP cancer patients, respectively. While feeling of incompetent and being less outgoing were the speech-related psychosocial concerns for 64.7% and 23.5% OC and 15.8% and 18.4% OP cancer patients, respectively. Worse speech outcomes were noted for oral tongue and base of tongue cancers vs. tonsillar cancers, mean (SD) values were 56.7 (31.3) and 52.0 (38.4) vs. 10.9 (14.8) (P<0.001) and late vs. early T stage cancers 65.0 (29.9) vs. 29.3 (32.7) (P<0.005). The English version of the SHI is a reliable, valid and useful tool for the evaluation of speech in HNC patients. Over one-third of OC and OP cancer patients reported speech problems in their day-do-day life. Advanced T-stage tumors affecting the oral tongue or base of tongue are particularly associated with poor speech outcomes.

First report on the reliability and validity of speech handicap index in native English-speaking patients with head and neck cancer.

BACKGROUND: Posttreatment speech problems are seen in nearly half of patients with head and neck cancer. Although there are many voice-specific scales, surprisingly there is no speech-specific questionnaire for English-speaking patients with head and neck cancer. The aim of this study was to validate the Speech Handicap Index (SHI) as the first speech-specific questionnaire in the English language. METHOD: In all, 55 consecutive patients in follow-up for oral and oropharyngeal cancer completed the SHI and University of Washington Quality of Life Questionnaire (UWQOL V.04). Thirty-two patients completed both questionnaires again 4 weeks later to address test-retest reliability. RESULTS: Internal consistency, test-retest reliability, construct validity, and group validity of the SHI were found to be highly significant (p < .01) using Cronbach's alpha, Spearman's correlation coefficient (r), and Mann-Whitney U tests. CONCLUSIONS: The SHI is a precise, highly reliable, and valid speech assessment tool for patients with head and neck cancer. Further dedicated studies using the SHI in patients with head and neck cancer would be useful.

Comprehensive review of small bowel metastasis from head and neck squamous cell carcinoma.

Secondary tumours of small intestine account for 10% of all small bowel cancers. The most common sites of primary tumour metastasizing to small bowel are uterus, cervix, colon, lung, breast and melanoma. The majority of these metastatic tumours come from adenocarcinoma primaries; squamous cell carcinoma constitutes a very small proportion of all metastatic small intestinal lesions. Metastasis to small bowel by head and neck squamous cell carcinoma is extremely rare and carries an unfavourable prognosis. Owing to the limited number of published studies, its characteristic features, clinical presentation and outcomes are poorly described. This work aims at specifying these characteristics by reviewing, compiling, analysing and reporting all published cases in the published literature on small bowel metastasis secondary to head and neck squamous cell carcinoma. To the best of our knowledge, this is the first comprehensive review article on the small intestinal metastasis from head and neck squamous cell carcinoma.

Validation of the Sydney Swallow Questionnaire (SSQ) in a cohort of head and neck cancer patients.

Impairment of swallowing function is a common multidimensional symptom complex seen in 50-75% of head and neck cancer (HNC) survivors. Although there are a number of validated swallowing-specific questionnaires, much of their focus is on the evaluation of swallowing-related quality of life (QOL) rather than swallowing as a specific function. The aim of this study was to validate the Sydney Swallow Questionnaire (SSQ) as a swallowing-specific instrument in HNC patients. Fifty-four consecutive patients in follow-up for oral and oropharyngeal cancer completed the SSQ and MD Anderson Dysphagia Inventory (MDADI). Thirty-one patients completed both questionnaires again four weeks later to address test-retest reliability. Internal consistency and test-retest reliability was assessed using Cronbach's alpha and Spearman's correlation coefficient, respectively. Construct validity (including group validity) and criterion validity were determined using Spearman's correlation coefficient and Mann-Whitney U-test. Internal consistency, test-retest reliability, construct validity, group validity and criterion validity of the SSQ was found to be significant (P<0.01). We were able to demonstrate the reliability and validity of the SSQ in HNC patients. The SSQ is a precise, reliable and valid tool for assessing swallow in this patient group.

Effect of penethamate hydriodide treatment on bacteriological cure, somatic cell count and milk production of cows and quarters with chronic subclinical Streptococcus uberis or Streptococcus dysgalactiae infection.

A randomized, controlled field trial was performed in The Netherlands to determine the therapeutic efficacy of parenteral penethamate hydriodide (Leocillin) against naturally occurring, chronic, streptococcal mastitis during lactation. Quarter milk samples were collected from subclinical cases of Streptococcus uberis or Streptococcus dysgalactiae mastitis to determine the effect of treatment on bacteriological cure and somatic cell count (SCC) at quarter level. A quarter was considered to be cured when the bacterial species, isolated prior to treatment, was not isolated from the quarter milk samples taken on days 10 and 20 post-treatment (bacteriological cure), or when a quarter milk SCC (QMSCC) was <250000 cells/ml on days 10 and 20 post-treatment (SCC cure). Longitudinal data analysis was performed to determine the effect of antibiotic therapy on SCC and milk yield at cow level. Bacteriological cure occurred in 59% of 29 treated quarters, while no cure was observed in any of the 21 untreated control quarters. Treatment resulted in a significant decrease in SCC at cow and quarter level in comparison with untreated controls. There was no significant effect of treatment on milk production. Antibacterial treatment of subclinical streptococcal infections during lactation also prevented clinical mastitis. Furthermore, the treatment may contribute to reduction of bulk milk SCC and to prevention of pathogen spread in dairy herds.