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Our aim is to describe a family with a nonsyndromic form of hereditary gingival fibromatosis (HGF) and discuss genetic characteristics of this rare disease by reviewing reported cases. A mother and three descendants were diagnosed with HGF. There was marked variable expressivity: from severe generalized gingival overgrowth in a 16-year-old boy (the proband) to minimal manifestations in the mother. The proband was submitted to gingivectomy and gingivoplasty. In younger siblings, the disease remained stable for 5 years, suggesting that clinical surveillance is a good option. The diagnosis was supported by histopathological examination. Analysis of this family and literature-reported cases supports that HGF most frequently shows an autosomal dominant inheritance with high penetrance and variable expressivity. Neomutations and gonadal mosaicism do not seem to be a rare event. Although five loci have been mapped by linkage analysis, only two genes, SOS1 and REST, were identified in four families.

Trail running involves off-road running over different surfaces of positive and negative unevenness. Given these particularities and the associated physical demands, it is essential to understand this relationship and how fitness levels influence performance. This study aimed to analyze fitness level variations during different times of the season and establish a relationship between changes in fitness levels and accumulated load. Twenty-five trail running athletes (age: 36.23 ± 8.30 years) were monitored over 52 weeks. Three periods of assessment were implemented, while load between those periods was calculated. Athletes were monitored daily by global positioning systems. The collected data included distance covered, duration, and rate of perceived exertion (RPE), which were used to obtain session-RPE. Additionally, maximal aerobic speed, vertical jump, and dynamic balance were tested periodically. Moderate inverse correlations were found between assessment 1 and 2 for total sRPE and vertical jump: countermovement jump (VJ: CMJ) (r = −0.349), and Y balance test: left posterolateral (YBT: LPL) (r = −0.494). Similar correlations were found between assessment 2 and 3 for total sRPE and VJ: CMJ (r = −0.397), and vertical jump: drop jump (VJ: DJ) (r = −0.395). The results suggest that trail running coaches should monitor and assess dose–response relationships and possible anterior asymmetries of dynamic balance performance.

Background The purpose of this study was to characterize trail running injuries within a cohort of Portuguese male and female recreational trail running athletes. Methods The study was retrospective (12 months), with data collected through an online survey. A total of 719 athletes participated (529 male and 190 female, average age: 38.01±7.78 years). A valid questionnaire was used to collect: 1) demographic information; 2) general information; 3) training typology; 4) physical information; 5) injuries (body location, number, type, reason, treatment, time without practice); and 6) general information concerning the effects of injuries on respondents' daily lives. Results The results revealed that 87.8% of the sample contracted an injury resulting from this practice, with the toenails (24.8%), knees (17.5%), and ankles (14.5%) being the most-often reported locations of injuries and blisters (20%), irritation (chafing) (14%), superficial wounds (12%), sprains (11%), and iliotibial band syndrome (7%) being the most common injuries. The result of 10.0 injuries per 1000 h was found, with a negative and medium correlation (r=-0.344; P=0.000) between total exposure time and injuries per 1000 h. It was also found that those who do not perform warm-up have a significantly increased injury rate (P Conclusions The gathered evidence demonstrated a large number of dermatological and musculoskeletal injuries, and these tended to have higher incidences in athletes with less exposure time and who devalue warm-up exercises.

The purpose of this study was to compare the variations of weekly workload indices of internal and external load measures across the three weeks prior to injury occurrences in trail runners. Twenty-five trail runners (age: 36.23 &plusmn, 8.30 years old, body mass: 67.24 &plusmn, 5.97 kg, height: 172.12 &plusmn, 5.12 cm) were monitored daily for 52 weeks using global positioning systems (GPSs) to determine the total distance covered. Additionally, a rate of perceived exertion (RPE) scale was applied to determine session-RPE (sRPE: RPE multiplied by training time). The accumulated load (AL), acute: chronic workload ratio (ACWR), training monotony (TM), and training strain (TS) indices were calculated weekly for each runner. During the period of analysis, the injury occurrences were recorded. The differences were observed in AL and ACWR for sRPE and training time were significantly greater during the injury week when compared to the previous weeks. Similar evidence was found in TM and TS indices for sRPE, training time, and total distance. Furthermore, no meaningful differences were observed in AL and ACWR for total distance in the weeks prior to injury occurrence. Nevertheless, significant between-subjects variability was found, and this should be carefully considered. For that reason, an individualized analysis of the workload dynamics is recommended, avoiding greater spikes in load by aiming to keep a progressive increment of load without consequences for injury risk.

SETTING Although cough in tuberculosis (TB) is presumed to be important for transmission, there is little objective supporting evidence. OBJECTIVE To describe 24-h cough frequency in a group with TB, and investigate associations with household rates of infection. DESIGN Patients with a new diagnosis of pulmonary TB underwent 24-h cough frequency measurement at or just before initiation of anti-tuberculosis treatment. A group with latent Mycobacterium tuberculosis infection (LTBI) acted as controls. Rates of infection among household contacts of sputum smear-positive TB were measured using the interferon-gamma release assay and the tuberculin skin test, and compared with variables relating to the contacts themselves, and to the index case, including cough frequency. RESULTS Daily cough frequency in TB patients (n = 44) was variable (geometric mean [GM] 174, interquartile range [IQR] 68-475 coughs/24 h), higher than in LTBI (n = 17; GM 19 coughs/24 h, IQR 8-53; P < 0.001), and higher during the day than overnight (GM 8.9 coughs/h, IQR 4.1-19.0 vs. GM 2.9 coughs/h, IQR 0.7-13.4; P < 0.0001). Also, 24-h cough frequency in TB was associated with sputum smear status (P = 0.040), but not smoking (P = 0.475). Multivariable logistic regression confirmed that infection in contacts was independently associated with index case sputum smear grade (P = 0.014) and cough frequency (P = 0.022). CONCLUSION Measurement of 24-h cough frequency in pulmonary TB helps predict infectiousness and transmission patterns.

Introduction Cough in bronchiectasis is associated with significant impairment in health status. This study aimed to quantify cough frequency objectively with a cough monitor and investigate its relationship with health status. A secondary aim was to identify clinical predictors of cough frequency. Methods Fifty-four patients with bronchiectasis were compared with thirty-five healthy controls. Objective 24-h cough, health status (cough-specific: Leicester Cough Questionnaire LCQ and bronchiectasis specific: Bronchiectasis Health Questionnaire BHQ), cough severity and lung function were measured. The clinical predictors of cough frequency in bronchiectasis were determined in a multivariate analysis. Results Objective cough frequency was significantly raised in patients with bronchiectasis compared to healthy controls [geometric mean (standard deviation)] 184.5 (4.0) vs. 20.6 (3.2) coughs/24-h; mean fold-difference (95% confidence interval) 8.9 (5.2, 15.2); p

Em Dezembro de 2019, o mundo assistiu à emergência de uma zoonose provocada por um novo tipo de Corona vírus o SARS CoV 2. Esta infeção rapidamente evoluiu para uma disseminação pandémica com consequências pesadas em todos os planos civilizacionais. O SARS CoV 2 e a Covid 19 persistem presentemente sem previsões para a sua eliminação, com grande incerteza sobre a sua evolução e extensão quer das consequências sanitárias quer do impacto económico. Desta forma importa desenvolver estratégias que possibilitem o funcionamento das estruturas produtivas, combatendo o congelamento económico e social enquanto consequências absolutamente nefastas no contexto pandémico. A Medicina Dentária, pela sua natureza, nomeadamente a produção de aerossóis, foi classificada como sendo uma atividade no topo do risco de aquisição/disseminação da doença por parte dos profissionais que a exercem. Muitos países suspenderam o exercício de Medicina Dentária como medida preventiva. Importa, pois, agora e na perspetiva de regresso criar mecanismos que permitam o exercício profissional em segurança. No entanto existe uma lacuna extensa sobre a própria definição de segurança no exercício profissional em Medicina Dentária no contexto SARS CoV 2 /Covid 19. O objetivo destas Normas de Orientação Clínica (NOC) foi compilar de forma sistematizada a evidência existente sobre esta temática e conferir a maior robustez possível à decisão clínica no pré per e pós consulta.

Em Dezembro de 2019, o mundo assistiu à emergência de uma zoonose provocada por um novo tipo de Corona vírus o SARS CoV 2. Esta infeção rapidamente evoluiu para uma disseminação pandémica com consequências pesadas em todos os planos civilizacionais. O SARS CoV 2 e a Covid 19 persistem presentemente sem previsões para a sua eliminação, com grande incerteza sobre a sua evolução e extensão quer das consequências sanitárias quer do impacto económico. Desta forma importa desenvolver estratégias que possibilitem o funcionamento das estruturas produtivas, combatendo o congelamento económico e social enquanto consequências absolutamente nefastas no contexto pandémico. A Medicina Dentária, pela sua natureza, nomeadamente a produção de aerossóis, foi classificada como sendo uma atividade no topo do risco de aquisição/disseminação da doença por parte dos profissionais que a exercem. Muitos países suspenderam o exercício de Medicina Dentária como medida preventiva. Importa, pois, agora e na perspetiva de regresso criar mecanismos que permitam o exercício profissional em segurança. No entanto existe uma lacuna extensa sobre a própria definição de segurança no exercício profissional em Medicina Dentária no contexto SARS CoV 2 /Covid 19. O objetivo destas Normas de Orientação Clínica (NOC) foi compilar de forma sistematizada a evidência existente sobre esta temática e conferir a maior robustez possível à decisão clínica no pré per e pós consulta.

Endurance sports like trail running constitute an extensive individual modality causing numerous physiological changes to occur in the athlete. In this sense, an adequate monitoring of training load appears to be essential to improve competition performance. The aim of this study was two-fold: (i) to analyze trail runners&rsquo, weekly load variations in the four weeks leading up to a trail running competition, and (ii) to determine the relationship between the runners&rsquo, pacing in competitions and their physical fitness and workload parameters. Twenty-five amateur male trail runners (age: 36.23 &plusmn, 8.30 years old, minimum International Trail Running Association performance index: 600) were monitored daily for the duration of a season (52 weeks). External load (distance covered, pace) and internal load (rate of perceived exertion) were measured daily. Additionally, weekly workload measures of acute:chronic workload ratio (ACWR), training monotony, and training strain were calculated. The runners were also assessed for maximal aerobic speed (MAS) every four months. No significant differences in workload measures (p &gt, 0.05) were observed in the four weeks leading up to each short trail competition, however, leading up to the long trail, ultra-trail medium, and ultra-trail long/extra-long competitions, the differences in the runners&rsquo, workload measures were significant (p &lt, 0.05). In the short trail, pace was found to be moderately correlated with the ACWR of total distance (r = &minus, 0.334) and with training monotony of rate of perceived exertion (RPE) (r = &minus, 0.303). In the ultra-trail, a large correlation was observed between pace and elevation accumulated (r = 0.677). We concluded that significant workload differences from one week to the next only occurred in preparation for longer-distance competitions, with sudden acute load decreases and very low ACWR values reported mainly in weeks 1 and 2 of the taper. Meaningful relationships were found between performance (pace) and MAS for longer trails and between pace and MAS for ultra-trail competitions.

Em Dezembro de 2019, o mundo assistiu à emergência de uma zoonose provocada por um novo tipo de Corona vírus o SARS CoV 2. Esta infeção rapidamente evoluiu para uma disseminação pandémica com consequências pesadas em todos os planos civilizacionais. O SARS CoV 2 e a Covid 19 persistem presentemente sem previsões para a sua eliminação, com grande incerteza sobre a sua evolução e extensão quer das consequências sanitárias quer do impacto económico. Desta forma importa desenvolver estratégias que possibilitem o funcionamento das estruturas produtivas, combatendo o congelamento económico e social enquanto consequências absolutamente nefastas no contexto pandémico. A Medicina Dentária, pela sua natureza, nomeadamente a produção de aerossóis, foi classificada como sendo uma atividade no topo do risco de aquisição/disseminação da doença por parte dos profissionais que a exercem. Muitos países suspenderam o exercício de Medicina Dentária como medida preventiva. Importa, pois, agora e na perspetiva de regresso criar mecanismos que permitam o exercício profissional em segurança. No entanto existe uma lacuna extensa sobre a própria definição de segurança no exercício profissional em Medicina Dentária no contexto SARS CoV 2 /Covid 19. O objetivo destas Normas de Orientação Clínica (NOC) foi compilar de forma sistematizada a evidência existente sobre esta temática e conferir a maior robustez possível à decisão clínica no pré per e pós consulta.

The present study aimed to analyze the relationship between variables related to the internal and external loads of training and competition races as well as to athletes' perceptions of well-being measured throughout the course of a 4-week mesocycle. It also aimed to analyze the intra- and inter-week variations in terms of training load and well-being. The study included the participation of 47 male recreational athletes competing in the national championships of trail running in Portugal (age: 34.85 ± 8.88 years; height: 1.77 ± 0.58 m; body mass: 65.89 ± 3.17 kg). During the 4 weeks, subjective perception of effort (RPE), training time (min), session-RPE (sRPE), distance covered (km), and perception of well-being (Hooper's questionnaire) were monitored. Weekly RPE was greater in week 1 than in week 3 (p = 0.001; d = 0.563, small effect). Moreover, weekly sRPE was greater in week 1 than in week 2 (p = 0.001; d = 0.441, small effect). The correlations between the well-being variables and RPE that were found to be significant with small magnitudes are those between sleep and RPE (r = 0.287; p = 0.001), stress and RPE (r = 0.217; p = 0.001), fatigue and RPE (r = 0.191; p = 0.001), muscle soreness and RPE (r = 0.240; p = 0.001), and Hooper's index and RPE (r = 0.279; p = 0.001). Among the variables of the Cooper test and the competition race load, it was verified that VO2max had a negative correlation of an average magnitude with pace (r = -0.396, p = 0.015). The findings of the study suggest that small variations in training stimulus during the period of analysis and increases in maximal oxygen uptake result in improvements in the performance of trail running athletes when considering the running speed in the race.

Cardiovascular diseases are the leading cause of death worldwide. These diseases are related with a broad range of factors but usually show high correlation with diminished left ventricle function, which can be evaluated by measuring the ventricular ejection fraction through transthoracic echocardiography (TTE), a cost-effective and highly portable first-line diagnosing technique. Ejection fraction (EF) is currently determined through a semi-automatic process that requires manual delineation of the left ventricle area both in a diastolic and systolic frame of the patient's exam. To remove this manual annotation step, which is both time-consuming and user dependent, automatic Computer-Aided Diagnosis (CAD) systems can be used. Herein, we propose the first steps for such a system that classifies ejection fraction in four classes, based on TTE exams, with the objective of automatically providing valuable information to physicians. Our classification method is based on a 3D-Convolutional Neural Network (3D-CNN) trained on a dataset constructed with exams from a cardiology reference center. The dataset creation consisted of three main steps: firstly, for each exam, cine-loops showing the apical 4 chambers view were manually selected; then, 30 sequential frames were extracted from each cine-loop; finally, each frame was pre-processed to mask burned-in metadata. The neural network was designed to explore concepts such as convolutions using asymmetric filters and residual learning blocks. The model was trained on a dataset with 4000 TTE exams and tested on a separate dataset containing 1600 TTE cases. We obtained an accuracy of 78% and a F1 score of 71.3% for unhealthy EF (below 45%), 63.3% for intermediate EF (45-55%), 72.3% for healthy EF (55-75%) and 54.6% for abnormally high EF (above 75%). These results are promising and show that convolutional neural networks can be applied to this domain. Furthermore, this work will serve as a foundation for future research where other relevant cardiac metrics will be determined.

Introduction: Objective cough frequency (CF) is an increasingly used to assess efficacy of antitussive therapy. CF has largely been investigated in clinical trials and research studies. We assessed CF in a large specialist cough clinic, and report its association with subjective measures of cough. Method: Patients with chronic cough (duration >8 weeks) underwent 24-hour cough monitoring prior to evaluation, with the validated, ambulatory, automated Leicester Cough Monitor. The subjects also completed a cough severity Visual Analogue Scale (0-100mm) and health status questionnaire (Leicester Cough Questionnaire; LCQ, range 3-21, better health = higher score). Results: Geometric mean (logSD) CF for all (n=320) and refractory cough (n=131) subjects was 11.56 (0.42) and 12.88 (0.40) c/h, respectively (Table 1). 46(27%) of all subjects and 11(8%) refractory cough subjects had a CF within the normal range ( Conclusion: CF monitoring can be integrated into clinical practice. This is the largest study of CF to date and CF was lower than that reported in clinical trials. This is useful for calculating the sample size for future studies.

BACKGROUND: The recent development of automated cough monitors has enabled objective assessment of cough frequency. A study was undertaken to determine whether short-duration recordings( < 6 h) accurately reflect 24-h cough frequency and to investigate their responsiveness. METHODS: One hundred adults with chronic cough underwent 24-h cough frequency monitoring with the Leicester Cough Monitor and completed cough visual analog scales (VASs) and the Leicester Cough Questionnaire (LCQ). Cough recordings were analyzed using customized software to derive cough frequencies from 1 to 6 h and 24-h recordings. Responsiveness was assessed with repeat assessments following therapeutic trials. RESULTS: The median (interquartile range) 24-h cough frequency was 11.5 (5.8-26.6) coughs/h. Four hours was considered the shortest recording duration that represented 24-h cough frequency( ρ= 0.9, P ≤ .001). Median 4-h cough frequency was 16.6 (7.3-36.8) coughs/h. Both 4-h and 24-h cough frequency correlated moderately with cough VAS ( ρ= 0.49, P ≤ .01 and ρ= 0.44, P ≤ .01)and LCQ ( ρ = - 0.48, P ≤ .01; ρ = - 0.50, P ≤ .01). Four-hour cough frequency was responsive to improvements in cough severity following trials of therapy. CONCLUSIONS: Four-hour cough frequency correlates highly with 24-h cough frequency recordings and relates equally well with subjective measures in chronic cough. Short-duration cough monitoring could be a practical tool to validate the presence of cough and assess response to trials of therapy in the clinic setting.

Background: This prospective, randomized, controlled clinical trial study compared the clinical outcomes of the biomaterial anorganic bovine-derived hydroxyapatite matrix/cell-binding peptide (ABM/P-15) as a biocompatible hydrogel carrier consisting of carboxymethylcellulose and glycerol or in particulate form when used as a bone replacement graft in the treatment of human periodontal infrabony defects. Methods: Nineteen patients with advanced chronic periodontitis were recruited. All patients had at least two non-adjacent intrabony osseous defects ‡3 mm after completion of cause-related periodontal therapy. The surgical procedures included access flaps for root instrumentation and filling the defect with ABM/P-15 in hydrogel or particulate form. Reentry access flap surgery was performed at 6 months. Changes in soft and hard tissue outcome measurements between baseline and 6 months were evaluated in all defects. Results: At 6 months, no significant differences between ABM/P15 hydrogel and ABM/P-15 particulate were demonstrated for the amount of defect fill (3.10 – 0.85 mm [75.0%] versus 3.09 – 1.11 mm [73.7%], respectively) or defect resolution (85.8% versus 81.9%). Changes in soft tissue clinical outcomes did not show significant differences between the treatments. Conclusion: This trial failed to demonstrate superiority of the novel ABM/P-15 hydrogel therapeutic modality over the standard ABM/ P-15 particulate graft in the treatment of intrabony periodontal defects. J Periodontol 2007;78:1855-1863.

The objective monitoring of cough for extended periods of time has long been recognized as an important step towards a better understanding of this symptom, and a better management of chronic cough patients. In this paper, we present a system for the automatic analysis of 24-h, continuous, ambulatory recordings of cough. The system uses audio recordings from a miniature microphone and the detection algorithm is based on statistical models of the time-spectral characteristics of cough sounds. We validated the system against manual counts obtained by a trained observer on 40 ambulatory recordings and our results show a median sensitivity value of 85.7%, median positive predictive value of 94.7% and median false positive rate of 0.8 events/h. An analysis application was developed, with a graphical user interface, allowing the use of the system in clinical settings by technical or medical staff. The result of the analysis of a recording session is presented as a concise, graphical-based report. The modular nature of the system interface facilitates its enhancement with the integration of further modules.

Background: Coughing is important in the transmission of tuberculosis (TB). It is not known if characteristics of cough in TB are distinct and whether they are clinically useful. Aims: To compare temporal patterns of coughing in TB to those in COPD and refractory chronic cough. Methods: Patients with stable COPD, refractory chronic cough and newly-diagnosed smear-positive pulmonary TB wore the Leicester Cough Monitor for 24 h. For TB, treatment was started either during or after the monitoring period. Cough frequency, nocturnal cough rates and cough clustering were calculated with the monitor9s automated algorithm and compared between diagnostic groups. Separation of coughs by >2 s defined the limits of a cough episode, consisting of either a lone cough or a bout of ≥2 cough sounds. Results: Median (IQR) cough counts in COPD (n=14), chronic cough (n=30) and TB (n=25) were 305 (128-462), 578 (215-1002) and 316 (101-700) per 24h, respectively (p=0.02). Nocturnal reductions in cough rates occurred to a similar extent in all groups; a mean (SD) of 24.5 (12.5), 20.4 (11.8) and 26.4 (19.2)% of coughs were detected overnight between 22:00 and 08:00, respectively (p=0.32). The clustering of coughs was not significantly different between groups: a mean (SD) of 42.0 (22.2), 29.2 (18.4) and 35.4 (19.3)% of episodes consisted of lone coughs rather than bouts (p=0.13), and the median (IQR) number of coughs per episode was 1.6 (1.4-2.0), 2.0 (1.7-2.5) and 1.7 (1.4-2.1), respectively (p=0.28). Conclusions: Coughing was less frequent in TB than refractory chronic cough, but of similar frequency to in COPD. There was no evidence of a difference in the temporal pattern of cough in TB compared to COPD and chronic cough.

To the Editor: Chronic cough is a difficult clinical problem, partly because there is an absence of well-validated means to assess cough [1, 2]. We have previously reported that the semi-automated computerised Leicester Cough Monitor detects cough accurately over 6 h and that cough frequency is increased in patients with chronic cough compared to controls [3, 4]. There remains uncertainty on the performance of the system over 24 h and across the range of expected cough frequency in larger populations. We set out to address these questions in healthy adult volunteers and adult volunteers with respiratory disease. 44 healthy volunteers were recruited from those responding to a poster advertisement. All reported no current respiratory symptoms, were nonsmokers with a

Objectives An ex vivo model was designed to profilometrically and histologically assess root changes resulting from scaling with a new ultrasonic device, designed for bone piezoelectric surgery, in comparison with curettes. Methods Three groups of 10 periodontal hopeless teeth were each subjected to different root instrumentation: Gracey curettes (CUR); ultrasonic piezoelectric device, Perio 100% setting, level 8 (P100); and ultrasonic piezoelectric device Surg 50% setting, level 1 (S50). After extraction, all teeth were photographed to visually assess the presence of dental calculus. The treated root surfaces were profilometrically evaluated (Ra, Rz, Rmax). Undecalcified histological sections were prepared to assess qualitative changes in cementum thickness. Statistical analysis was carried out using one-way anova test with a significance level of 95%. Results Both instruments proved to be effective in the complete removal of calculus. The CUR group presented the lowest Ra [2.28 μm (±0.58)] and S50 the highest [3.01 μm (±0.61)]. No statistically significant differences were detected among the three groups, for Ra, Rz and Rmax. Histologically, there was a cementum thickness reduction in all groups, being higher and more irregular in S50 group. Conclusions Within the limits of this study, there were no statistically significant differences in roughness parameters analyzed between curettes and the ultrasonic piezoelectric unit. This new instrument removes a smaller amount of cementum, mainly at the Perio 100% power setting, which appears to be the least damaging. The ultrasonic device is effective in calculus removal, proving to be as effective as curettes.

With the proliferation of social networks and blogs, the Internet is increasingly being used to disseminate personal health information rather than just as a source of information. In this paper we exploit the wealth of user-generated data, available through the micro-blogging service Twitter, to estimate and track the incidence of health conditions in society. The method is based on two stages: we start by extracting possibly relevant tweets using a set of specially crafted regular expressions, and then classify these initial messages using machine learning methods. Furthermore, we selected relevant features to improve the results and the execution times. To test the method, we considered four health states or conditions, namely flu, depression, pregnancy and eating disorders, and two locations, Portugal and Spain. We present the results obtained and demonstrate that the detection results and the performance of the method are improved after feature selection. The results are promising, with areas under the receiver operating characteristic curve between 0.7 and 0.9, and f-measure values around 0.8 and 0.9. This fact indicates that such approach provides a feasible solution for measuring and tracking the evolution of health states within the society.

Novel Nanocrystalline Hydroxyapatite for Bone Regeneration Maxillofacial bone defects resulting from disease or trauma are one main problem for modern dentistry. Regenerative treatments aim to provide the lost initial conditions improving the patient’s life quality. Bone graft substitutes have been regarded as suitable alternatives to obtain regenerative outcomes. Among these, synthetic hydroxyapatites are successfully evaluated bone substitutes, both in pre-clinical as well as clinical studies. The aim of this study is to evaluate the bone regenerative potential of a nanocrystalline hydroxyapatite (nHA), in a delayed healing cranial rabbit model.

RATIONALE: Cough can be assessed with visual analog scales (VAS), health status measures, and 24-hour cough frequency monitors (CF(24)). Evidence for their measurement properties in acute cough caused by upper respiratory tract infection (URTI) and longitudinal data is limited. OBJECTIVES: To assess cough longitudinally in URTI with subjective and objective outcome measures and determine sample size for future studies. METHODS: Thirty-three previously healthy subjects with URTI completed cough VAS, Leicester Cough Questionnaire (LCQ-acute), and CF(24) monitoring (Leicester Cough Monitor) on three occasions, 4 days apart. Changes in subjects' condition were assessed with a global rating of change questionnaire. The potential for baseline first-hour cough frequency (CF(1)), VAS, and LCQ to identify low CF(24) was assessed. MEASUREMENTS AND MAIN RESULTS: Mean ± SD duration of cough at visit 1 was 4.1 ± 2.5 days. Geometric mean ± log SD baseline CF(24) and median (interquartile range) cough bouts were high (14.9 ± 0.4 coughs/h and 85 [39-195] bouts/24 h). Health status was severely impaired. There was a significant reduction in CF(24) and VAS, and improvement in LCQ, from visits 1-3. At visit 3, CF(24) remained above normal limits in 52% of subjects. The smallest changes in CF(24), LCQ, and VAS that subjects perceived important were 54%, 2- and 17-mm change from baseline, respectively. The sample sizes required for parallel group studies to detect these changes are 27, 51, and 25 subjects per group, respectively. CF(1) (

Introduction Patterns of cough in tuberculosis influence transmission of disease yet have been little studied. We report the prevalence, duration, severity and frequency of coughing in tuberculosis. Method The first part was a retrospective review of the medical records of all individuals diagnosed with pulmonary tuberculosis (PTB) at our hospital during 2012–3. The reported presence and duration of coughing was noted. In the second part of the study, successive patients with an ultimate diagnosis of PTB wore the Leicester Cough Monitor for 24 h prior to commencing treatment. Controls had latent TB infection (LTBI). Participants rated their cough severity from 0–100 with a visual analogue scale (VAS). Cough characteristics were compared with other clinical variables. Results 108 cases of PTB from 2012–3 were included. 82 reported cough of median (IQR) duration 4 (1–8) weeks. There was a significant association of the presence of cough with TB sputum culture positivity (odds ratio, 11.0; 95% confidence interval, 2.5–50.0) but not gender, smoking, smear positivity, cavitary disease or extent of radiographic change. No clear predictor of the duration of cough was identified and there were too few patients to estimate the effect of TB strain. Cough frequency was measured in subjects with sputum smear positive PTB (S+; n = 20), smear negative PTB (S-; n = 10) and LTBI (n = 11). Variability was high: median (IQR) cough rates were 238 (121–701), 126 (15–395) and 11 (7–56) coughs/24 h, respectively, and not significantly different for S+ vs. S- (figure). For active TB, cough rates were reduced overnight (2.8 [0.2–12.4] vs. 12.7 [3.3–23.4] coughs/h for night vs. day, respectively; p = 0.01). No effect of smoking was detected, nor was there a correlation between cough frequency and radiographic extent of disease, cavities or time to sputum culture positivity. Cough severity was higher for S+ than S- but also variable and the difference not statistically significant (VAS: 60 [13–94] vs. 22 [1.5–70] respectively; p = 0.41). Severity correlated with cough frequency in active tuberculosis (Spearman’s r = 0.60, p = 0.001). Conclusion Cough in TB reduces overnight and is related to culture positivity. Bacterial burden and extent of disease may not be important. Other determinants of cough await characterisation.

AIMS: Unexplained chronic cough is a common condition with no satisfactory treatments. Previous work has suggested that cough may be linked to neutrophilic airway inflammation. This study tested the hypothesis that long-term low-dose erythromycin reduces the induced sputum neutrophil count and 24 h cough frequency in patients with unexplained chronic cough. METHODS: 30 patients with an unexplained chronic cough lasting more than 8 weeks were randomly assigned to take 250 mg erythromycin once daily (n=15) or placebo (n=15) for 12 weeks in a double-blind parallel group study. Cough frequency, cough reflex sensitivity and cough severity were assessed at baseline, 6, 12 and 24 weeks. The primary outcome measure was change in 24 h cough frequency at 12 weeks. RESULTS: There was no difference in the change in cough frequency between the erythromycin and placebo groups at 12 weeks (mean difference in fold change 1.1; 95% CI 0.7 to 1.5; p=0.585) or at other times. There was a statistically significant between-treatment difference in the change in sputum neutrophils at 12 weeks (−10.2% vs +6.6% with erythromycin and placebo; mean difference 16.8%; 95% CI 1.6 to 32.1; p=0.03) but not at other times. There was no difference in the change in other measures of cough between treatments. CONCLUSIONS: Treatment with low-dose erythromycin for 12 weeks reduces the induced sputum neutrophil count but not cough frequency or severity in patients with unexplained chronic cough.

P-15 is a synthetic 15-amino acid residue identical to the cell binding domain of type I collagen. P-15 can be adsorbed onto anorganic bovine bone mineral (ABM) and will enhance cell attachment and subsequent cell activation. Although ABM/P-15 has been studied as a bone graft substitute in the oral cavity, its use in orthopedic models has been limited. Thus, this study investigated the efficacy of ABM/P-15 treatment in a rabbit model of long bone cancellous healing. Defects were created in the distal femurs and proximal medial tibiae of rabbits and were filled with either ABMP/P-15 suspended in hydrogel, ABM alone suspended in hydrogel, hydrogel carrier alone, or no graft material. Rabbits were sacrificed at 1, 2, 4, or 8 weeks postsurgery, and the femurs and tibiae were harvested. Histomorphometric analyses indicated that defects treated with ABM/P-15 had significantly larger areas of new bone formation than the other three treatments at 2 and 8 weeks postsurgery. ABM/P-15 treated defects also had significantly more bone growth than defects left empty or filled with ABM alone at 4 weeks postsurgery. Furthermore, histological examination did not reveal acute inflammatory infiltrate cells in any of the treatment conditions. These results are consistent with the findings of ABM/P-15 use in human oral-maxillofacial studies and in large animal spine fusion models.

Chronic cough is a common reason for presentation to both general practice and respiratory clinics. In up to 25% of cases, the cause remains unclear after extensive investigations. We report 4 patients presenting with an isolated chronic cough who were subsequently found to have obstructive sleep apnoea. The cough improved rapidly with nocturnal continuous positive airway pressure therapy. Further studies are required to investigate the prevalence of coexistence of these common conditions.

Cough is a common symptom of many respiratory diseases. The evaluation of its intensity and frequency of occurrence could provide valuable clinical information in the assessment of patients with chronic cough. In this paper we propose the use of hidden Markov models (HMMs) to automatically detect cough sounds from continuous ambulatory recordings. The recording system consists of a digital sound recorder and a microphone attached to the patient's chest. The recognition algorithm follows a keyword-spotting approach, with cough sounds representing the keywords. It was trained on 821 min selected from 10 ambulatory recordings, including 2473 manually labeled cough events, and tested on a database of nine recordings from separate patients with a total recording time of 3060 min and comprising 2155 cough events. The average detection rate was 82% at a false alarm rate of seven events/h, when considering only events above an energy threshold relative to each recording's average energy. These results suggest that HMMs can be applied to the detection of cough sounds from ambulatory patients. A postprocessing stage to perform a more detailed analysis on the detected events is under development, and could allow the rejection of some of the incorrectly detected events.

Summary Background Little is known about the frequency of cough in health and in patients with chronic cough. Methods We measured cough frequency and its relationship with other markers of cough severity in 20 patients with chronic cough and 9 healthy subjects using the Leicester Cough Monitor (LCM), which is an automated ambulatory digital cough monitor that records sound only. All subjects had a 6-h recording and recordings were manually counted. A subgroup of 6 normals and 6 patients with a stable chronic cough had repeat measurements up to 6 months apart. Results Mean ( sem ) cough counts/hour were 43(8) in patients with chronic cough and 2(1) in normals (mean difference 41; 95% confidence interval 24–59; P 0.001 ). The cough counts were repeatable (within subject standard deviation: 23 coughs/hour; intraclass correlation coefficient 0.8). Cough counts correlated significantly with physical ( r = - 0.6 , P = 0.03 ), social ( r = - 0.7 , P = 0.01 ) and total Leicester Cough Questionnaire (LCQ) health status scores ( r = - 0.6 , P = 0.03 ) and cough sensitivity (concentration of capsaicin causing 5 coughs: r = 0.9 , P = 0.008 ). Conclusion We have shown that there are marked differences in cough frequency between patients with chronic cough and healthy subjects, that these measurements are repeatable, and that they correlate with cough-specific health status.

Introduction Acute cough is a common illness with more than 12 million episodes each year in the UK. More than £100 million is spent on over-the-counter cough medicines annually, despite limited evidence to support their efficacy. The optimal cough assessment outcome parameter for clinical evaluation of anti-tussive drugs is not known. We investigated the natural course of acute cough with objective and subjective cough assessment tools. Methods 32 healthy subjects with acute cough due to upper respiratory tract infection (median (IQR) age 30 (32–35) years, 63% female, mean (SEM) duration of cough 4.2 (0.4) days) were recruited for evaluation. Subjects taking anti-tussives were excluded. Assessments of cough severity included objective 24-h ambulatory cough frequency monitoring with the Leicester Cough Monitor, health related quality of life (HRQOL) with the Leicester Cough Questionnaire-Acute (LCQ) and cough severity visual analogue scale (VAS). Assessments were performed at baseline (day 1) and then 4 and 8 days later. Global rating of change questionnaires were completed by patients at each follow-up to assess change in cough severity and determine minimal important difference. Results At baseline, the median (IQR) LCQ score was 14.7 (10.9–18.3) and mean (SEM) cough VAS was 48 (4) mm, consistent with a severe cough associated with significant impairment in HRQOL. Geometric mean (logSD) 24-h cough frequency (CF 24 ) at baseline was 15.0 (0.4) coughs/hr, and at days 5 and 9 were 8.7 (0.5) and 3.4 (0.7) coughs/hr respectively. At day 5, 3 subjects reported no change, 9 mild, 14 moderate and 6 large change in their cough severity. At day 9, 6 subjects reported mild, 5 moderate and 20 large change in cough severity. The minimal important difference on day 5 for the LCQ was 2.0, VAS 17 mm and CF 24 54% change from baseline. Conclusions Acute cough is associated with a significant cough frequency and impairment in HRQOL. We suggest clinical trials of anti-tussive drugs should incorporate objective and subjective cough assessment outcome measures. Anti-tussive drugs need to demonstrate a considerable reduction in cough frequency (>54% over a 4-day interval) to establish clinically important efficacy.

Introduction Cough is the unique respiratory symptom. Although associated with a range of conditions it has been little studied in acute respiratory disease. We describe cough frequency and cough-related quality of life in this group. Method Participants had a diagnosis of acute exacerbation of asthma (asthma), chronic obstructive pulmonary disease (AECOPD), or lower respiratory tract infection (including community-acquired pneumonia) in the absence of the other respiratory disease (LRTI). Quality of life was measured with the Leicester Cough Questionnaire (LCQ-acute), cough severity with a visual analogue scale (VAS) and 24-hour cough frequency with the Leicester Cough Monitor. Results 40 patients were recruited within a median (interquartile range) of 1 (1–2.3) day ( ) of hospital admission. Median (IQR) age was 57 (41–71) and 63% were female. Geometric mean ± log 10­ SD cough frequencywas high: 19.7 ± 1.36, 33.8 ± 2.02 and 23.6 ± 1.31 coughs/h for asthma (n = 11), AECOPD (n = 15) and LRTI (n = 14) respectively (Figure); median (IQR) cough bouts/24h: 81 (54–210), 148 (97–197) and 129 (67–197). There was no significant difference between disease groups in these values (p > 0.05 for all two-way comparisons). Diurnal variation and median numbers of coughs/ bout were similar between groups. The 48% of patients who were current smokers coughed more than non-smokers (33.6 ± 1.91 vs 20.2 ± 1.38 coughs/h, p = 0.07). No difference in cough frequency was detected amongst the 25% taking angiotensin converting enzyme inhibitors. Gender had no significant overall effect. Median (IQR) VAS scores were 39 (32–86), 73 (53–100) and 82 (48–91) for asthma, AECOPD and LRTI respectively with no significant difference between them. Cough severity showed a significant correlation with 24-hour cough frequency overall (Spearman’ coefficient 0.33, p = 0.05). LCQ-acute scores were lower for LRTI (8.4; 6.4–9.5) than asthma (14.7; 10.7–17.5); p = 0.01 (Figure 1). Neither was significantly different from those for AECOPD (11.5; 8.5–15.6). Quality of life did not correlate with cough frequency (Spearman’ coefficient -0.13; p = 0.48). Conclusion Cough frequency in acute respiratory disease is high but with high variation. Cough frequency accounts for only part of morbidity in these conditions.

Introduction and Objectives Cough sound analysis is currently used for the assessment of cough frequency; it is not known if it could be used to assess cough intensity. We investigated the optimal Cough Sound Intensity (CSI) measure by validating it against peak cough flow rate (PCFR). Methods 17 (11 female) patients with stable chronic cough and 15 (8 female) healthy subjects underwent simultaneous measurements of peak cough flow rate and cough sound during voluntary coughs using 2 types of microphones. Subjects were asked to cough voluntarily 10 times at 5 incremental thoracic pressures as measured by an oesophageal balloon catheter. Visual feedback was given to patients. A range of CSI parameters were determined from the cough sound signal. CSI was calculated for the actual cough sound duration and also for a constant duration (time constant) to assess the potential for automation. The repeatability of CSI and the effect of microphone position were assessed. For each subject, PCFRs and CSI data were normalised to values obtained during maximum voluntary cough (MVC). Results The correlation between the optimal CSI and peak cough flow rate was best for the free-field microphone; median (IQR) correlation coefficient 0.88 (0.79–0.92) (Table 1). The median correlation for all cough sound intensity remained strong for males (r=0.90–0.91), females (r=0.79–0.84), patients with chronic cough (r=0.79–0.82) and healthy subjects (r=0.82–0.89). The intraclass correlation coefficient for repeatability was good, r=0.90, p Conclusion Cough sound intensity correlates strongly with PCFR in voluntary cough and is a repeatable measure. The microphone position needs to be standardised as in this study. Further work is needed to automate the analysis of CSI; our preliminary findings suggest this is possible. The CSI has the potential to be developed into a non-invasive, ambulatory outcome measure of cough severity.

Introduction 24-hour cough frequency monitoring is increasingly being used as an outcome measure to evaluate anti-tussive drugs. The optimal method of identifying patients with a significant cough frequency for inclusion into clinical trials is not known. We investigated a range of cough assessments screening tools that could be used for this purpose. Methods 35 healthy subjects with acute cough due to upper respiratory infection (median (IQR) age 31 (23–35) years, 63% female, median (IQR) duration of cough 4 (2–6) days) were recruited as part of a larger study. All subjects underwent ambulatory 24-h cough frequency (CF 24 ) monitoring with the Leicester Cough Monitor, health related quality of life with the Leicester Cough Questionnaire-acute (LCQ) and cough severity visual analogue scale (VAS). Receiver operating characteristic curve analyses were performed for the baseline screening tools LCQ, VAS and cough frequency in first hour (CF 1 ) to identify patients with CF 24 =5, =7.5 and =10 coughs/hr. Results The baseline geometric mean (logSD) CF 24 was 14.7 (0.5) coughs/hr, CF 1 25.9 (0.4) coughs/hr, mean (SEM) VAS 47 (3) mm and LCQ 14.3 (0.7). 4, 6 and 11 patients had CF 24 24 were poor, ranging from 0.51 to 0.58 and 0.50 to 0.68 respectively. The mean (SEM) AUC for CF 1 was 0.92 (0.05), 0.79 (0.10) and 0.86 (0.06) for detecting 24-h cough frequency of =5, =7.5 and =10 coughs/hr respectively. The sensitivity and specificity for cough frequency recordings over 1 h to identify patients with significant 24-h cough frequency are presented in Abstract S140 table 1. A good specificity (to exclude patients with low 24-h cough frequency) was achievable at sensitivities ranging from 69 to 87%. Conclusion Subjective cough severity and cough-specific quality of life are poor screening tools for predicting objective 24-h cough frequency. However, 1-h cough frequency can be used as a screening tool to identify patients with significant 24-h cough frequency for inclusion into future clinical trials.

The tremendous quantity of data stored daily in healthcare institutions demands the development of new methods to summarize and reuse available information in clinical practice. In order to leverage modern healthcare information systems, new strategies must be developed that address challenges such as extraction of relevant information, data redundancy, and the lack of associations within the data. This article proposes a pipeline to overcome these challenges in the context of medical imaging reports, by automatically extracting and linking information, and summarizing natural language reports into an ontology model. Using data from the Physionet MIMIC II database, we created a semantic knowledge base with more than 6.5 millions of triples obtained from a collection of 16,000 radiology reports.