Objectives: To explore periimplant health  4-5 years after implant insertion.Study Design: A practice-based dental research network multicentre study was performed in 11 Spanish centres. The first patient/month with implant insertion in 2004 was considered. Per patient four teeth (one per quadrant) showing the highest bone loss in the 2004 panoramic X-ray were selected for periodontal status assessment. Bone losses in implants were calculated as the differences between 2004 and 2009 bone levels in radiographs. Results: A total of 117 patients were included. Of the 408 teeth considered, 73 (17.9%) were lost in 2009 (losing risk: >50% for bone losses ≥7mm). A total of 295 implants were reviewed. Eight of 117 (6.8%) patients had lost implants . Implant loss rate (quadrant status) was 1.4% (edentulous), 3.6% (preserved teeth), and 11.1% (lost teeth) (p=0.037). The percentage of implant loss significantly (p<0.001) increased when the medial/distal bone loss was ≥3 mm. The highest (p≤0.001) pocket depths were found in teeth with ≥5mm and implants with ≥3mm bone losses, with similar mean values (≥4mm), associated with higher rates of plaque index and bleeding by probing. Conclusions: The significant bi-directional relation between plaque and bone loss, and between each of these two parameters/signs and pocket depths or bleeding  together with the higher percentage of implants lost when the bone loss of the associated teeth was ≥3 mm suggest that the patient’s periodontal status is a critical issue in predicting implant health/lesion. Key words:Implants, periimplantitis, periodontitis, oral health, practice-based research Periodontitis can be considered the consequence of broken balances in bacterial components of the plaque . Its prePractice-based dental research networks have been used to identify problems in “real-life” dental practice . In restThe aim of this practice-based dental research network study was to explore peri-implant health  4-5 years after implant insertion, using parameters measured in daily practice  in a series of patients not selected based on clinical diagnoses.A multicentre study was carried out in 2009 in 11 Spanish dental clinics to assess implant health conditions in patients with at least one implant installed in 2004. To avoid selection bias, centres were asked to include the first patient of each month (except August) with implant insertion in 2004. Patients were contacted by phone and were asked to voluntarily participate by attending the clinic for a revision including X-ray. If the patient was not able or declined to attend the visit, the second patient of the month with implant insertion was contacted. The protocol from the Spanish Society for Implants  was followed, and a case report form was used to collect data from 2004  and 2009 (in the revision visit). Examiners (one per centre) were instructed for data collection to minimize inter-center variations. The study protocol was approved by the Ethics Committee of Hospital Clinico Universitario San Carlos, Madrid, Spain (CP-CI 10/140-E).Demographic data, general health conditions, co-morbidities , habits , treatment with biphosphonates, and dental bruxism were noted from clinical records in 2004 and updated in 2009. The four teeth (one per quadrant and not removed for implant insertion) showing the highest bone loss in the panoramic radiograph performed in 2004 prior to implant insertion were used as index sites for the assessment of the periodontal status of each patient. Bone levels at their mesial and distal aspects were determined by assessing the distance between the most coronal position of the supporting bone and the cement-enamel junction with the use of a transparent ruler scaled . If the Data from teeth and implants recorded at the revision visit in 2009 consisted in: plaque index  , pocket Case report forms were sent for double data entry using SPSS v.14 . Comparisons of quantitative variables were performed by the t-test or ANOVA tests, using Tuckey test for comparisons of two groups. Correlations between quantitative variables were calculated by the Spearman (non-parametric) correlation test. Qualitative variables were compared by the Chi-square or Fisher’s exact test when necessary. Multivariate analyses were performed by multiple linear regression in order to explain the role of bone loss  and plaque index  on pocket probing depths as dependent variable. An independent analysis was performed for each of the six measuring sites of pocket probing depths, and both for teeth and implants. In order to avoid false associations in multiple comparisons, p<0.01 was considered significant.Characteristics of patientsNine centres included 11 patients each, one centre included 10 patients and the remaining centre included eight patients. A total of 147 patients were phoned and 30 patients failed to be contacted or refused to participate. A total of 117 patients  were included in the study. Of them, 37.6% were smokers, 17.1% ex-smokers, 26.5% presented mild to moderate alcohol intake, 24.9% bruxism, 6.0% diabetes and 4.3% cardiovascular disease. A total of 64 (54.7%) patients had attended the previous annual dental revisions.In 2004, 84.6% patients presented teeth in the four quadrants, 1.7% patients in three quadrants, 4.3% patients in two quadrants, 0.9% patients in one quadrant, and 8.5% patients were completely edentulous.The risk of losing teethA total of 408 teeth were identified in the panoramic X-ray performed in 2004 as those with the highest bone loss per quadrant: 30.1% were at position 7, 21.6% at 6, 13.0% at 5, and 35.3% at other positions. There was a significant correlation between values of bone loss at mesial and distal sites, both globally and per quadrant . Correlations were also found between mesial values  in the four quadrants, as well as between distal values . Globally, values of bone loss at distal sites were higher than those at mesial sites (3.77 ± 2.04 vs. 3.61 ± 2.07), although differences tended to be significant only in the upper quadrants (p=0.003 for quadrant 1 and p=0.05 for quadrant 2). Of the 408 teeth identified for the study (present in 2004), 73 (17.9%) had been lost when patients attended the revision in 2009. No relations could be found between tooth loss and the recorded demographic or health conditions, although the relation between tooth loss and bruxism was almost significant (p=0.012) since higher number of patients among those that lost teeth from 2004 to 2009 presented bruxism (40.5% vs. 17.7%).Fig. The risk of losing implantsA total of 295 implants were installed in 2004 in the 117 patients included in the study. There were 36.8% patients with one implant installed, 24.8% with two, 12.8% with three, 13.7% with four, 4.3% with five, and 7.7% patients with ≥6 implants installed. Of the 295 implants, 30.5% were installed in quadrant 1 (Q1), 24.7% in quadrant 2 (Q2), 19.7% in quadrant 3 (Q3) and 25.1% in quadrant 4 (Q4). Overall, positions 5 and 6 were the most frequent for implant insertion, accounting for 45.1% of all implants. Of the 295 implants, 31 (10.5%) were installed immediately after dental extraction. Regenerative techniques were used in 17.3% (51 out of 295) of implant insertions. Complete reconstruction was carried out in 27.4% patients, using fixed dental prostheses in 90.4% of the 295 implants. Reconstructions were friction-retained in 9.9% implants, cemented in 32.5% implants and screw-retained in 57.5% implants. Casted plastic burnout abutments were used in 43.2% implants, machined titanium abutments in 35.0%, and casted-on premachined palladium abutments in 21.8%.In the 2009 revision visit, 8 out of 117 (6.8%) patients had lost implants: four patients lost one implant, three patients lost two implants and one patient lost three implants. The 13 lost implants represented 34.2% of the 38 implants installed in these eight patients in 2004. All patients that lost implants had multiple (from 3 to 6) implants installed in 2004. On a patient basis there was a tendency for significance for a greater percentage of lost implants in patients with multiple implant installed (8 out of 74 patients) versus in those with one implant installed (0 out of 43): 10.8% vs. 0% (p=0.026). This tendency disappeared when the analysis was performed on implant basis: 0 out of 43 for single implant insertion vs. 5.2% (13 out of 252) for the number of implants in patients with multiple implants installed (p=0.600).Of the 13 out of 295 (4.4%) implants that were lost, 24.5% and 19.9% corresponded to positions 6 and 5, respectively. In Q2, 8.2% implants were lost, 6.9% in Q3, 2.7% in Q4 and 1.1% in Q1.Is there a relationship between teeth (and their bone levels) and implant losses?Among edentulous quadrants in 2004, the percentage of implant loss was 1.4% (1 out of 73). This percentage of implant loss increased to 3.6% (6 out of 168) in quadrants where teeth were preserved from 2004 to 2009 and to 11.1% (6 out of 54) among quadrants losing teeth in the same period (p=0.037).The relation of implant loss with the bone loss (in the X-ray in 2004) for the associated teeth in the quadrant could be analysed in 12 of the 13 implants lost (one lost implant was in an edentulous quadrant). No significant correlation  was found between medial bone losses for the associated teeth and implant losses, but the percentage of implant loss significantly (p<0.001) increased from 0.93% (2 out of 215) when the medial bone loss was <2 mm to 36.0% (9 out of 25) when it was ≥3 mm. Neither significant (p=0.097), although high (r2=0.626), was the correlation with distal bone loss values for associated teeth, the percentage of implant loss also significantly (p<0.001) increasing from 0.0% (0 out of 206) when the distal bone loss was <2 mm to 28.6% (6 out of 21) when it was ≥3 mm.Periodontal health in preserved teethIn the 335 study teeth (those identified in the panoramic X-ray performed in 2004 and remaining in 2009), mean pocket probing depths were: 3.4 ± 1.7 mm for mesio-vestibular (MV), 2.8 ± 1.6 mm for vestibular (V), 3.6 ± 1.7 mm for disto-vestibular (DV), 3.3 ± 1.6 mm for mesio-lingual (ML), 2.8 ± 1.6 mm for lingual (L), and 3.5 ± 1.6 mm for disto-lingual (DL), without differences between quadrants. A significant correlation was found between values measured at the different sites . Plaque was visible in 25.3% (85 out of 335) teeth, with significant lower percentage of teeth with visible plaque in upper than in lower quadrants . Mobility was described in 24.8% teeth, bleeding on probing in 59.7%, and suppuration in 2.7%.  shows clPeri-implant health in preserved implantsOf the 282 implants that remained in function in 2009 , full data was available for 268 implants. Mean peri-implant marginal bone loss (considered as the difference between the bone level in 2004 and the bone level in the X-ray in 2009) was 0.9 ± 1.1 mm for mesial and 1.0 ± 1.2 for distal values, with significantly (p=0.001) lower values in the right side for distal measures (0.8 ± 0.9 mm for Q1+Q4 vs. 1.2 ± 1.3 mm for Q2+Q3). No significant differences were found between upper and lower quadrants.Pocket probing depths were: 2.6 ± 1.5 mm for MV, 2.1 ± 1.2 mm for V, 2.6 ± 1.4 mm for DV, 2.6 ± 1.4 mm for ML, 2.2 ± 1.3 mm for L, and 2.6 ± 1.4 mm for DL. A significant correlation was found between values measured at the different sites . Values in the right side tended to be higher than those in the left side for MV .Plaque was visible in 13.4% (36 out of 268) implants, with lower percentage of implants with visible plaque in right than in left quadrants . Bleeding on probing was found in 54.9% implants.  shows clIs there a relationship between clinical parameters from preserved teeth and implants? Significantly higher percentage of teeth than implants presented plaque (grouping plaque visible + plaque present by probing): 65.1% vs. 45.9%; p<0.001  and plaqSignificant (p<0.001) correlations in pocket probing depths were found between implants and the associated teeth in the same quadrant: r2=0.35 for MV, r2=0.55 for V, r2=0.36 for DV, r2=0.40 for ML, r2=0.47 for L, and r2=0.36 for DL.The role of bone loss and plaque index on pocket probing depthsFor teeth, the multivariate analysis was significant (p<0.001), with r2 ranging from 0.35 to 0.47 depending on the pocket depth measuring site. Pocket probing depths were significantly correlated with plaque index  and bone loss .In the case of implants, although statistical significance was reached (p<0.001) in the model, the overall predictability was lower (r2 from 0.055 to 0.218). Pocket probing depths were significantly correlated with bone loss  but not with plaque index .In Odontology disease definitions rely on measures of probing depth, bone loss and bleeding on probing . In the Some authors indicate that patients with periodontitis may experience more implant loss than non-periodontitis patients ,16,17 baAnother interesting finding was that, on a patient basis, there was a tendency for significance for a greater percentage of lost implants in patients with multiple implant installed versus in those with one implant installed (10.8% vs. 0%). This could be interpreted as consequence of the worse periodontal status of patients receiving more than one implant, confirming once more the analogy of periodontitis and peri-implantitis and the global healthy/unhealthy per-patient condition in the studied patients. However there is a strong confounding factor (more implant loss when more implants are inserted) since when the analysis is performed on implant basis, the tendency disappeared since there were not differences between implant lost in single installations (0%) and in multiple installations (4.4%).Several definitions of peri-implant disease are found in the literature ,16,21,22The relative importance of microbial factors and mechanical forces as cause of peri-implantitis remains controversial. Through performing an explicative multivariate analysis we tried to determine the role of bone loss and plaque index (as independent variables) on pocket probing depths (as dependent variable), both for teeth and implants. Significant correlations were found for both independent variables and pocket depths in teeth, but in implants significant correlations were only found for bone loss. The discussion on the importance of microbial and mechanical factors in the depth of pockets as well as for bone loss may be academic since in clinical practice, as shown in this study, bone loss is associated with deepening of pockets that intuitively create an increasing anaerobic environment colonised by intra-oral translocation of periodontal pathogens from teeth showing chronic periodontitis. This may contribute to a further marginal bone loss , althougPractice-based dental research network studies based on clinical parameters/signs used in daily practice may be helpful in investigating indices for prediction of teeth survival (thus indicating when to insert an implant) and the survival of implants. The results of the present study, where the periodontal status was assessed by clinical parameters of the tooth with the highest bone loss at baseline, showed the significant bi-directional relation between plaque and bone loss, and between each of these two parameters/signs with pocket depths and bleeding on probing, both in teeth and implants, and between them. This fact and the higher percentage of implants lost when the bone loss of the associated teeth was ≥3 mm reinforces the idea that the periodontal status of the patient is a critical issue in predicting implant health/lesion and that parameters measured in daily practice  may provide quantitative values for assessing longevity of implants. Further prospective studies are needed to conclusively confirm correlations, especially in relation to cutoff values of bone loss to define peri-implantitis.


P = 0.0013). The group of malignancy was subdivided in papillary thyroid carcinoma (PTMC) versus thyroid cancer of larger size (TCLS). Mean TSH was 1.71 ± 1.52 in PTMC and 2.42 ± 2.5 in TCLS. Significant differences were found when all groups  were compared (P < 0.001). However, pairwise comparisons between them showed that differences were only significant between benign and TCLS groups (P < 0.01). In conclusion, TSH levels were higher in patients with a final diagnosis of DTC. Moreover, it appears that there exists an increment in tumor size as a function of increment in the TSH level.We evaluated the preoperative serum thyrotropin (TSH) levels in 386 patients operated on for nodular thyroid disease (NTD). TSH levels for cases with final benign disease and differentiated thyroid carcinoma (DTC) were compared. No evidence of cancer was detected in 310 patients (80.3%), whereas malignancy was present in 76 cases (19.7%). Mean TSH concentration was 1.36 ± 1.62 mU/L in benign patients and 2.08 ± 2.1 in cases with malignant lesions ( Treatment of differentiated thyroid carcinomas (DTCs) includes total thyroidectomy, followed by removing affected (and nonaffected) lymph nodes in the central compartment of the neck, radioiodine for ablation of thyroid remnants or metastases, and suppressive treatment with L-thyroxine . A supraFurthermore, in recent years it has been shown that serum TSH concentration is an independent predictor of thyroid malignancy . SeveralThe present study was conducted to determine the preoperative serum TSH levels in a group of patients who underwent surgery for NTD. TSH concentrations were correlated with the final histological diagnosis, defined as the presence or absence of malignancy. Moreover, the group of malignancies was subdivided between patients with PTMCs and patients with thyroid cancers of larger size (TCLS).From January 2006 to December 2009, 438 patients underwent thyroid surgery for NTD. Patients (i) with known thyroid cancer, (ii) without an available serum TSH concentration within 1 year before surgery, (iii) with a final histological diagnosis other than DTC , and (iv) hyperthyroidism due to the Graves disease were not included. Three hundred eighty-six patients were eligible for the study.All patients had a solitary thyroid nodule or a multinodular goiter detected by clinical examination, ultrasound scan (US), or both. Preoperatively, thyroid USs confirmed NTD in all cases. A fineneedle aspiration biopsy (FNAB) was performed for thyroid nodules > 1 cm, or nodules < 1 cm with suspicious US features. Thyroidectomy was prescribed for patients with malignant, suspicious, or repetitive indeterminate nodules according to FNAB results. Moreover, surgery was indicated for benign disease when local symptoms were present or for esthetic reasons. All patients had a serum TSH level within 1 year before surgery measured by an automated immunochemiluminescent assay . The normal range was 0.4–4.0 mU/L. t-test was used for numerical variables. The Fisher's exact test was used for categorical variables. The nonparametric Kruskall-Wallis test was used to determinate whether there were significant differences between patients with benign, PTMCs, and TCLS. Afterwards, Bonferroni's adjustment for multiple comparisons was applied to the pairwise comparisons of groups. Values were reported as the mean ± SEM. A P value < 0.05 was considered statistically significant.Statistical analysis was performed to determinate whether or not there were differences in age and TSH levels between patients diagnosed with benign lesions, compared with those diagnosed with thyroid cancer. Furthermore, the group of patients with malignancies was subdivided into PTMCs and TCLS. Age was evaluated as a continuous variable. The TSH concentration was evaluated as a continuous variable and categorically within the following 3 ranges: <0.4 mU/L ; 0.4–4.0 mU/L (euthyroidism); >4.0 mU/L . The Student's There were 386 patients who met the inclusion criteria. The final pathology data showed no evidence of malignancy in 310 patients (80.3%), whereas malignant lesions were present in 76 cases (19.7%). The benign group included 250 females (80.6%) and 60 males (19.4%). The mean age at the time of diagnosis was 54.4 ± 14.2 years. There were 247 (79.7%) patients with multinodular goiter and 63 (20.3%) patients with thyroid nodule. Histological features of chronic thyroiditis were present in 75 (24.2%) patients. P = 0.005). There were 45 (59.2%) patients with multinodular goiter and 31 (28.2%) patients with thyroid nodule. Histological features of chronic thyroiditis were present in 18 (23.7%) patients. In the cohort of patients with malignancies, PTMCs were demonstrated in 36 patients (47.3%) and TCLS in the remaining 40 patients . The mean age in the patients with PTMCs was 52.1 ± 14.7 years, and 46.8 ± 13.8 years in the patients with TCLS. DTC was diagnosed in 60 females (78.9%) and 16 males (21.1%). The mean age at the time of diagnosis was 49.3 ± 14.4 years. There was a significant difference in age between both groups (P = 0.0013). Thus, the TSH levels were higher in patients with a final diagnosis of DTC. Among the set of patients with malignant nodules, mean TSH was 1.71 ± 1.52 mU/L in patients with PTMCs and 2.42 ± 2.5 mU/L in patients with TCLS. Statistical significance was found when the three groups  were compared (P < 0.001). However, pairwise comparisons between them showed that differences in TSH were only significant between benign and TCLS groups (P < 0.01).P = 0.027). In contrast, 8 patients (10.6%) with thyroid cancer were diagnosed with subclinical hypothyroidism (TSH > 4 mU/L), whereas this profile existed in 11 patients (3.5%) with benign lesions (P = 0.01). In summary, in patients with subclinical hyperthyroidism, normal TSH concentration and subclinical hypothyroidism malignancy rate were 12%, 20.5%, and 42%, respectively, (Seventy-four (23.9%) patients with benign nodules were classified as subclinical hyperthyroidism (TSH < 0.4 mU/L). This diagnosis was only detected in 10 patients (13.1%) with malignancies . Among this last group, mean TSH level was 1.75 ± 0.8 mU/L in patients with PTMCs and 1.84 ± 0.9 mU/L in patients with TCLS. Again, these differences were not significant. However, the TSH levels were significantly different between the group with benign lesions and a normal TSH level and patients with TCLS and a normal TSH level (P = 0.026). Finally, there were not significant differences among groups related to the presence of chronic thyroiditis.When we excluded all patients with TSH out of the normal range, the association between the TSH level and the final histology remained significant. The mean TSH level in the 225 patients with no evidence of malignancy and a normal TSH was 1.47 ± 0.8 mU/L, whereas the mean TSH level in the 58 patients with malignancies was 1.8 ± 0.8 mU/L . To our knowledge, the present paper is the first study that has not only compared TSH concentrations in patients with benign and malignant lesions, but also in PTMCs and TCLS. We have confirmed that the TSH level is significantly different between benign nodules and DTCs. These differences have persisted when comparing benign lesions and carcinomas > 1 cm in size, and when comparing all three groups. It appears that there exists an increment in tumor size as a function of increment in the TSH level. Thus, benign lesions have the lowest TSH levels, PTMCs have intermediate concentrations, and DTCs of larger size are associated with the highest levels of TSH. However, though the escalatory increment of TSH between the three groups of patients is evident, statistical analysis shows that differences are not significant, probably due to the small number of cases with cancer. According to these results, we suggest that TSH participates in the carcinogenesis of PTC, it is possibly that it acts as a growth factor and could be one of the parameters that determines the size of DTCs. In this regard, recently, Franco et al.  have fou It is interesting to note that in our cohort, all patients underwent thyroid surgery. Thus, diagnoses of DTCs or benign thyroid disease were based on surgical pathologic results in all of the cases analyzed. In contrast, the diagnosis was established with FNAB results in other series without confirmatory histological results. For example, in the study by Boelaert et al. , only 37Unfortunately, information about thyroid antibodies was not analysed because there were no data in approximately one quarter of patients. However, histological preparations were examined, in order to verify the presence or not of autoimmune chronic thyroiditis. In this regard, we did not observe any differences between groups. Finally, it is well known the predominantly benign nature of thyroid autonomous nodules. Moreover, in patients with autonomous nodules, TSH concentrations were decreased or suppressed. In our study, the association between TSH level and final histology remained significant after patients with subclinical hypo- and hyperthyroidism were excluded. In summary, we have shown that TSH levels were higher in patients with a final diagnosis of DTC. Moreover, it appears that there exists an increment in tumor size as a function of increment in the TSH level. Although the role of the TSH level in the development and/or progression of thyroid cancer remains controversial, our results support the hypothesis that the TSH level might be involved in the progression, that is, the size, of an existing DTC.Authors declare no conflict of interests.


Slow waves originate from the pacemaker network of the interstitial cells of Cajal (ICC) and determine the direction and velocity of propagation of peristaltic activity of the gastrointestinal (GI) tract. The enteric nervous system (ENS) and smooth muscle cells are known to interface with ICCs through excitatory and inhibitory neurotransmitters. Electrogastrography (EGG) can be used to record gastric myoelectrical activity (GMA) and reveals slow wave information, in terms of frequency and power. GMA has been studied in conscious rabbits, dogs, rats, and ferrets, but rarely in mice. Nicotine was used to activate ganglia in an attempt to modulate excitatory and inhibitory neurons linked to ICC functioning. The aim of the present study, therefore, was to define the characteristics of GMA in mice, and to establish criteria for analysis.® ETA-F20, DSI) with recording wires sutured from the serosal surface of the stomach. 7 days later, baseline GMA recordings were obtained 2 h before injecting animals with nicotine , or vehicle . Recordings then continued for a further 6 h. Raw data (sampled at 1000 Hz) were analyzed using Spike2 . A low pass FIR filter was applied  to eliminate cardiac/respiratory signals. The waveform was then interpolated to 10.24 Hz before applying the second low pass FIR filter . The resultant waveform was then processed further by Fast Fourier Transformation (FFT) to yield components of frequency. Two-way repeated measures ANOVA was performed to compare between the 8 vehicle- and 8 drug-treatment mice. A value of P<0.05 was considered statistically significant.16 male ICR mice  were anaesthetized and surgically implanted with telemetry devices (PhysioTelThe dominant frequency (DF) of the baseline recordings of the vehicle and nicotine treatment groups were 6.8 ± 0.4 and 6.6 ± 0.4 counts per min (cpm), respectively. For the baseline recording of the vehicle and nicotine treatment groups, 40.9-41.8 % of the power was in the normogastric range (DF ± 2 cpm). 9.1-9.7 % and 26.6-26.6 % of the power was in the bradygastric (0 to DF-2 cpm) and tachygastric ranges (DF+2 to 15 cpm), respectively. Saline had no effect on slow waves during the experiment . Nicotine reduced the DF almost immediately to 5.9 ± 0.5 cpm  and produced a no-significant increase in % power of bradygastria (P>0.05). The effects of nicotine lasted for 2 h before the DF shifted back to pre-nicotine levels (6.8 ± 0.4 cpm). The % power in tachygastria (DF+2 to 15 cpm) was not affected by nicotine (P>0.05).Nicotine, which is known to stimulate ganglia, caused bradygastria, suggesting an action to release inhibitory mediators to affect ICC. The studies demonstrate that radiotelemetry can be used to record GMA in conscious, freely moving mice, providing a convenient method to study GI functioning in a variety of circumstances. The studies were supported by a Direct Grant for Research (2006.2.034).


With evolutions in surgical techniques, minimally invasive surgical (MIS) repair with Achillon applicator has been introduced. However, there is still a lack of literature to investigate into the clinical merits of MIS over open surgery. This study aims to investigate the correlation between clinical outcome, gait analysis and biomechanical properties comparing both surgical methods.A single centre retrospective review on all the consecutive operated patients between January 2004 and December 2008 was performed. Twenty-six patients  had experienced a complete Achilles tendon rupture with operative repair. Nineteen of the patients, 10 MIS versus 9 open repairs (13 men with a mean age of 40.54 ± 10.43 (range 23-62 yrs) and 6 women with a mean age of 45.33 ± 7.71 (range 35-57 yrs) were further invited to attend a thorough clinical assessment using Holz's scale and biomechanical evaluation at a mean of 25.3 months after operation. This study utilized the Cybex II isokinetic dynamometer to assess the isokinetic peak force of plantar-flexion and dorsiflexion of both ankles. The patients were also invited to return to our Gait Laboratory for analysis. The eight-infrared camera motion capture system  was utilized for the acquisition of kinematic variables. Their anthropometric data was measured according to the Davis and coworkers' standard.The mean operative time and length of hospital stay were shorter in the MIS group. The operative time was 54.55 ± 15.15 minutes versus 68.80 ± 18.23 minutes of the MIS group and Open group respectively (p = 0.045), whereas length of stay was 3.36 ± 1.21 days versus 6.40 ± 3.70 days respectively (p = 0.039). There is statistically significant decrease (p = 0.005) in incision length in MIS group than the open surgery group, 3.23 ± 1.10 cm versus 9.64 ± 2.55 cm respectively. Both groups attained similar Holz's scores, 11.70 ± 0.95 versus 12.0 ± 1.50 respectively (p = 0.262). The mean percentage stance time of the injured leg for MIS patient was 58.44% while the mean percentage stance time of the injured leg for patients with open repair was 56.57%. T-test has shown there were no significance differences between the results of the two groups of patients. The loss of peak torque and total work done with respect to the injured side were similar between the MIS and open group.MIS using Achillon method can achieve smaller incisions, shorter operative time and hospital stay. There is no statistical significance difference in clinical outcome, the stance time to strike time ratio and biomechanical properties on the leg receiving Achilles tendon repair using MIS method and open surgery. Achilles tendon rupture most commonly occurs during recreational sports that require bursts of jumping, pivoting, and running. The incidence rate of Achilles tendon ruptures accounted for an overall mean of 8.3 ruptures per 100,000 people . AchilleThe recovery course can be variable and prevent patient to return to sports to the full. Operation is the treatment of the choice to enhance tendon approximation and tendon healing but conventional open repair can bring complications including wound infections, skin tethering, sural nerve damage, hypertrophic scars are not uncommon, accounting for 4-19% of patients ,4-6. SomMinimally invasive surgical (MIS) repair with Achillon applicator has been proven to be a safe and effective method for the management of for Achilles tendon rupture. The merits of minimally invasive surgical repair with Achillon applicator include limiting exposure of tendon, decreasing chance of sural nerve injury, reducing amount of suture material, allowing closure of paratenon and enhancing blood supply to facilitate maximal wound healing ,9. TheseHowever, parameters assessing the functional recovery after an Achilles tendon rupture are few and not well investigated. It has been shown that an incomplete functional recovery exists despite good results in terms of overall outcome and patients' satisfaction -12. Of nThe purpose of this study is to retrospectively investigate and compare MIS repair with Achillon device with open method in terms of plantar flexor muscle-tendon unit properties and the gait pattern in Chinese patients who underwent surgical repair of Achilles tendon rupture, by means of a multidisciplinary approach with clinical assessment, biomechanical evaluation and gait analysis.The hypothesis of this study is that patients from the MIS group can have shorter skin incisions, less wound infection, shorter operative time and shorter hospital stay than Open group.A single centre retrospective case series study on all the consecutive patients undergoing surgical repair of primary Achilles tendon rupture between January 2004 and December 2008 in AHNH was performed. The patients were divided into two groups, the MIS and the other being the open repair group, for further comparison. Patients' age, gender, laterality, type of sport involved, mechanism of injury, occupation, symptoms at presentation, dominant injury versus non-dominant limb injury, physical findings, radiological findings, operative findings, procedure undertaken, operative duration, surgical complications , clinical outcome and length of hospital stay were retrieved from medical records. Patients were further invited through telephone to return to hospital for further single-observer clinical assessment, single-observer gait analysis and single-observer biomechanical study.Exclusion criteria of this study included patients not being able to attend the assessments and those who did not undergo operative treatment for Achilles tendon rupture. From the data retrieved from our department, all the patients admitted during the study period were surgically fit for operation. After discussing treatment options of operative versus non-operative management, all the patients opted for surgical repair for the tendon ruptures.The operations were performed under general anaesthesia in a prone position. A tourniquet was always used over the thigh with exsanguination. A single dose of 1 g cephalosporin prophylactic antibiotic was administered on induction.A straight skin incision starting from the medial aspect of the heel up to the middle of the calf, preserving the lesser saphenous vein and the sural nerve, was made . The par8 A stab incision through the paratenon was made over the ruptured site, with both ends exposed. The haematoma was debrided. 3 Ethibond 2 sutures were passed through the holes of Achillon applicator, and tightened at full plantarflexion. The paratenon was then closed with Vicryl sutures with skin closed in layers.The operations were performed using the Achillon suture guide as first described by Assal et al, with the use of a U-shaped device with 4 limbs for tendon approximation.The postoperative management of all the subjects were the same. For the first 2 weeks after surgery, a short-leg cast was applied with the ankle in 20° equines position. The cast was then changed to an ankle walker for 2 weeks, and patients were allowed to increase weight-bearing gradually. Sport activities were not allowed for 3 months after the operation. Patients were followed up at 2 weeks, then monthly.This was performed by the principal investigator of this study, an Orthopaedic surgeon. Patients were requested to sign an informed consent form for participation of this study. A questionnaire had to be further filled in, particularly document dominant versus non-dominant limb injury. The dominant limb was defined as the limb preferred to execute a manipulative or mobilizing action while the non-dominant limb provide stabilizing support . The recGait analysis was performed by the same investigator, a Research Assistant from the Department of Orthopaedics and Traumatology, the Chinese University of Hong Kong, using the eight-infrared camera motion capture system  at 120 Hz for the acquisition of kinematic variables. Two Kistler platforms  were used to acquire ground reaction forces. Subjects were instructed to walk at a self-selected speed along a level surface approximately 10 m in length and practise until they could consistently and naturally make contact with both the force platforms. Five trials were acquired for each subject. The stride duration, stance phase and swing phase duration, as well as step length of both the injured and un-injured side were measured.The Cybex II+ isokinetic dynamometer with dual channel recorder and Cybex data reduction computer (CDRC), Upper Body Exercise Table (UBXT), and plantarflexion footplate were used in this study  to assess the final isokinetic peak force of plantar flexion of both ankles was applied when the patients had returned to their pre-injury activity level .All subjects were required to begin testing with a prescribed warm-up programme. The Cybex set-up and positioning for plantar-flexion were in accordance with the Cybex isolated joint testing manual and with the knee in a fully extended position (0°). All adjustments were made by the same Physiotherapist of Physiotherapy Department, AHNH. Three submaximal and two maximal peak force records were taken from the injured and uninjured ankle by the same physiotherapist to eliminate inter-observer errors.-1 and 180° s-1. Testing at 60° s-1 included five repetitions of exercise, while 25 consecutive repetitions were performed at 180° s-1. The isokinetic measures tested and utilized for the statistical analysis included peak torque at 60° s-1 and 180° s-1 and total work (TW) of the injured as well as un-injured side. In order to measure the difference of the ankle flexors, torque ratio and work ratio (dorsiflexor/plantar-flexor) were calculated. Ankle dorsiflexion and plantarflexion range were also measured. Peak torque and TW are given in Newton-metres (Nm) and AP in watts.Testings were carried out at speeds of 60° sWith the assumption that the parameters sampled from populations from normal distribution, the variances of the MIS and Open groups are unknown, the parameters are simple, randomly selected and independent, the 2-independent sample t-test was applied. Let a = 0.05, and 95% Confidence Interval for the mean difference. All the data collected upon assessments were further subjected to the checking of normality of data.This research protocol was submitted to the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC). The ethics approval of the research protocol was adopted from the CREC with reference number CRE-2009. 197 in May 2009, titled "Gait analysis following surgery for Achilles tendon rupture: Comparison of open repair with minimally invasive repair". Biomechanical studies and gait analysis were then conducted in compliance with the research regulations.A total of 26 patients  were identified within the study period and mean age of 42.1 years (range 23-62 years). 15 patients belonged to the Open group while another 11 patients were operated by MIS technique. Three of the patients underwent ultrasonographic investigation demonstrating a gap sign of the Achilles tendon, corresponding to complete rupture of the tendon. All the rest 19 patients were operated based on clinical findings of gap sign and also positive Simmond's test.A large majority of patients (42.3%) were recreational badminton players, followed by soccer 19.2%), basketball (11.5%), volleyball (3.9%) and jogging (3.9%) , mean age of 42.05 years (range 23-62 years) enrolled for further clinical assessment, gait analysis and biomechanical assessment. This included 10 MIS group patients and 9 Open group patients. Seven patients were excluded because 6 patients were lost due to change of contact telephone number and address, and 1 patient was unable to attend due to work in China. The mean age of the 10 MIS group patients was 41.70 years (range 29-57 years) whereas the mean age of the 9 Open group patients was 42.44 years (range 23-62 years). On questionnaire survey, 6 of the recruited 19 patients had seen bone setter with a mean 4.67 days delay (range 0-10 days) between injury and admission to our hospital. The remaining 10 patients, not having been seen by bone setter, had a mean 2.77 days delay  between the injury and admission to our hospital.The mean days between injuries and admission to our hospital were 5.20 days (range 0-30 days) versus 1.33 days (range 0-4 days) in the MIS group and Open group respectively. The documented number of days between injuries and operations were 8.90 days (range 3-30 days) and 5.78 (range 1-8 days) respectively. The interval between operation and clinical assessment was 12.00 months (Range 6-19 months) and 40 months (Range 6-62 months) for the two groups respectively.Not all patients presented with pop sound during injury. Combination weakness and pop sound were the most common initial symptoms, accounting for 31.6% (6/19) patients Table . Less coSixty percent (6/10) of the MIS group suffered from dominant side injury while only 33.3% (3/9) of patients in the OPEN group suffered from ruptured Achilles tendon on the dominant side, with p value being equal 0.370 on Fisher's Exact Test. As the study population was less than 50, Shapiro-Wilk test for normality was utilized for normality testing. With a = 0.05, Effect size d = 0.5, with MIS group number being equal to 10, Open group equal to 9, the power of the study was 0.1769673 by using G*Power 3.1.2 software (Heinrich Heine Universität Düsseldorf).Patients from the MIS group benefited from shorter operative time, 54.55 ± 15.15 minutes (range 35-90 minutes), with the contrary of 68.80 ± 18.23 minutes (range 40-100 minutes) in the Open group, with statistically significance (p = 0.045)  versus a mean length of 9.64 ± 2.55 cm (range 5.8-12.0 cm) in the Open group, with statistical significance difference (p = 0.005)  versus 1.113 ± 0.124 m (range 1.044-1.172 m) respectively (p = 0.378) Table . The meaThe maximal range of ankle movement measured showed similar findings with respect to plantarflexion as well as dorsiflexion were similar between the MIS and Open groups Table . Mean ma-1, the value of the injured side was 74.78% of the uninjured side in the MIS group as compared to 82.04% of the uninjured side in the Open group (p = 0.664). At 180° s-1, the peak torque of the injured side was 88.1% of the unaffected side in plantarflexion in the MIS group and 96.0% in the Open group (p = 0.896). For the mean peak torque in dorsiflexion at 60° s-1, the injured side showed 105.11% of the uninjured side for the MIS group and 86.46% for the Open group (p = 0.348). At 180° s-1, the peak torque in dorsiflexion of the injured leg was 92.5% of the normal side in the MIS group and 84.2% in the Open group (p = 0.493). An example of the peak torque output curves are put up in Figure The loss of peak torque and total work done with respect to the injured side were similar between the MIS and open groups Table  and 8. FMIS technique using Achillon applicator has fulfilled the goal of MIS with shorter wound incisions, shorter operative time and length of hospital stay in our study. However, the study population is small. A better study would be a prospective cohort study. In a regional hospital, the number of cases of ruptured Achilles tendon with operation done was less than 10 per year, the accumulation and collection of adequate cases for analysis might took years. Besides, there was no standardized interval between operation and postoperative assessments. As listed previously, the interval between operation and assessments of the Open group was much shorter than the MIS group. The Open group has stopped the rehabilitative physiotherapy long before the conduction of the assessments. This might bring systematic bias to the study results. With regard to the reasons above, a multi-centre prospective cohort study has been carried out to better delineate the benefits of MIS surgery over Open surgery.The mean operative time and length of hospital stay were shorter in the MIS group. The operative time was 54.55 ± 15.15 minutes versus 68.80 ± 18.23 minutes of the MIS group and Open group respectively (p = 0.045), whereas length of stay was 3.36 ± 1.21 days versus 6.40 ± 3.70 days respectively (p = 0.039). There is statistically significant decrease (p = 0.005) in incision length in MIS group than the open surgery group, 3.23 ± 1.10 cm versus 9.64 ± 2.55 cm respectively. Both groups attained similar Holz's scores, 11.70 ± 0.95 versus 12.0 ± 1.50 respectively (p = 0.262). The mean percentage stance time of the injured leg for MIS patient was 58.44% while the mean percentage stance time of the injured leg for patients with open repair was 56.57%. T-test has shown there were no significance differences between the results of the two groups of patients. The loss of peak torque and total work done with respect to the injured side were similar between the MIS and open group.The authors declare that they have no competing interests.CAPH, CYY, FDTP, LHY, LCK, YPSH, FKY, CHAN KM were involved in the study design and coordination. LHY, LCK and CAPH were involved in the operative treatments of the patients. CAPH conducted the medical record retrievals, establishment of questionnaire and clinical assessments. CYY carried out gait analysis and WONG PY carried out the biomechanical assessments. CAPH, CYY, FDTP conducted the statistical analysis. All authors read and approved the final manuscript.


The primary objective of this study was to determine whether local and imported cigarette brands used in , have elevated levels of metals or not. The produced data of cigarette brands are compared both with each other and with the existing brands in different countries.In present study, nineteen various cigarettes brands were randomly purchased from the commercially available cigarettes in Iranian market (Birjand city) including local Iranian branded and imported cigarettes. All samples were analyzed for heavy metals, viz. Cd, ,Cu ,Co Ni, Zn and Pb by graphite furnace atomic absorption spectrophotometer after microwave-assisted wet digestion method with nitric and perchloric acids. The observed average metals concentrations for cadmium in all cigarette brands was 2.71 and ranging 1.76 to 3.20, copper 9.7 (5.18-17.6), cobalt 4.42 with range of 2.57-6.49, nickel 17.93 (10.0-30), zinc 27.02 (18.1-42.2) and value for lead was 2.07 with range of 1.05 to 3.10 (µg/g dry weight) and mean metals content per cigarette was also measured. The produced data of imported and local cigarette brands are discussed and compared together and with studies from elsewhere. The investigation may confirm that the level of metal contents in Iranian cigarettes is similar to the other parts of the world. However, the concentration of these metals was slightly higher in comparison with other investigation. Some of the trace metals in biological samples derive from their essentiality, as well as from their potentially toxic effects in living organisms. That is, pollution due to heavy metals has acquired importance, since these metals are highly toxic for humans and for the whole ecology. 12  with physiological and neurological effects -12. AccoThere are a number of inorganic toxic elements and essential element present in tobacco along with organic carcinogens. Tobacco plant is open to absorb and accumulate heavy metal species from the soil into its leaves  or deposet al in 1983  were collected to make fresh data and measure six heavy metals . The produced data of imported and local cigarettes are discussed and compared with each other and with the existing ones in different countries.Instrumentation and reagentsVarian spectra 800 were coupled with GTA 100 electro thermal atomizer unit, graphite furnace atomic absorption spectrometer was used to determine the concentrations of metals. The temperature program and recommended parameters for trace elements at this instrument technique have been shown in A Sartorius analytical balance , Filter Paper Circles 110 mm diameter (ashless-Germany), PTFE (Polytetrafluoroethylene) vessel, microwave  were employed throughout the procedure. Agate ball mixer mill  such as Wiley mill, was used for grinding the cigarette tobacco. Sieves made of nylon with mesh sizes of Ø <65 were used to study the influence of particle size on extraction.All chemical material was used of Merck company. The Teflon boxes and plastic boxes were washed with 200 ml acid acetic 65% plus 5000 ml bidistilled water, and volumetric flasks with 50 ml acid acetic 65% plus 5000 ml bidistilled water, then they were washed two times with distilled water to remove any contamination. Preparation of tobacco samplesNineteen different brands of commonly sold cigarette in Iran market were randomly purchased from both imported (n= 11) and locally manufactured cigarettes (n= 8) (Table 3). Four packs of different batch number (for purpose of random sampling) and five of each composite batch of all branded cigarettes under study was used. For analysis of trace elements in cigarette tobacco, we separated all components of cigarette, tobacco, filter and wrapping paper of cigarettes. The average weight of each cigarette was determined by weighing 5 sticks of each brand whose means was about 1.02 g, and 82 mm in length.As soon as practicable after collecting, tobacco samples are commonly dried in a beaker, then grounded in an agate grinder (300 rpm) and sieved to obtain a < 65 µm fraction.Conventional acid digestion method. It is very strong acid digestion that will dissolve almost all elements that could become environmentally available.The method of acid digestion of solid samples is a total digestion technique for most samples. Digestion with acid or acid mixtures has long been the traditional method for the determination of metals in plants3 (65%) and HCl (37%) with a ratio of 4:1 (v/v) by heating them in microwave (wet-ashed) under high pressure (200 Atm) by 180 °C for 12 hr as described by Feldmann  was placed in a PTFE vessel and allowed to digest with a mixture of acidified with 10 ml of HNOFeldmann . PTFE boAnalysis of standard reference materialsValidation of the trace element measurements n tobaccos was performed in laboratory by analysis of standard reference materials to confirm the method used for the analysis of heavy metals. Reference standards for tobacco are few. In this investigation, in order to control the accuracy and the reproducibility of the chemical measurement process has been evaluated by analyzing certified samples of Pine Needles and Orchard Leaves from the United States National Bureau of Standards.All samples were analyzed for heavy metals, viz. Cd, Cu, Co Ni, Zn and Pb by Graphite furnace atomic absorption spectrophotometer (Varian spectra 800) in µg/g dry weight (DW).Statistics The original data were processed by one way ANOVA analysis and Microsoft Excel software to evaluate statistical model. Student’s t-test was used for the statistical analysis of the differences in heavy metals between imported and local cigarettes samples. The statistical evaluation of factors investigated was carried out using the Statistical Package for Social Sciences . The results of reference standards for tobacco were in good agreement with the certified values for trace metals and are shown in The precision of the method was studied on two different types of cigarettes, local and imported cigarettes sold in . The metals including lead, nickel, copper, cobalt, zinc and cadmium contents of several cigarette tobacco products are listed in Local cigarettes had a mean cadmium concentration 3.12 µg/g (DW) with a standard deviation of 0.06 whereas imported brands showed a cadmium concentration average 2.47 µg/g (DW) with a standard deviation of 0.41 µg/g. These results were followed by lead, copper, cobalt, zinc and nickel 2.27±0.27, 13.04±2.99, 4.58±1.2, 29.4±7.7 and 22.41±5.4 µg/g for local brands and 1.69±0.44, 7.8±2.3, 4.33±1.3, 25.6±5.03 and 15.32±4.7 µg/g for imported cigarettes respectively. Therefore, higher concentration of cadmium, nickel, copper and lead were observed in local cigarette brands as compared to imported cigarette brands. On other hand, among cigarette brands, the highest concentration of cadmium element were found in Sima , , Mond  (imported cigaretts) and Bahman with 3, 05 µg/g , whereas lowest cadmium content was in Lavan and cigarettes with 1, 76 and 1, 95 µg/g, respectively.The content of trace elements per cigarette was also calculated based on weighing each cigarette . It is sThe concentration of metals in both cigarette brands group follows almost the same trend; Zn > Ni > Cu > Co > Cd> Pb. et al  in comparison with local brands (coefficient of variation of 1.98% for cadmium and 10.14% for lead). Such inner brand variations in trace element concentration of tobacco products have been observed by others as well , 33. Howet al  also repet al  , 35, UK et al , Massadel  in comparison with studies in Japan , EthiopiIt has been published in different studies , 42, 44 et al  than the non-smokers.


Inherited ichthyoses represent a group of rare skin disorders characterized by scaling, hyperkeratosis and inconstant erythema, involving most of the tegument. Epidemiology remains poorly described. This study aims to evaluate the prevalence of inherited ichthyosis (excluding very mild forms) and its different clinical forms in France.Capture – recapture method was used for this study. According to statistical requirements, 3 different lists  were used to record such patients. The study was conducted in 5 areas during a closed period.The prevalence was estimated at 13.3 per million people (/M) . With regard to autosomal recessive congenital ichthyosis, the prevalence was estimated at 7/M (CI 95% [5.7 – 9.2]), with a prevalence of lamellar ichthyosis and congenital ichthyosiform erythroderma of 4.5/M (CI 95% [3.7 – 5.9]) and 1.9/M (CI 95% [1.6 – 2.6]), respectively. Prevalence of keratinopathic forms was estimated at 1.1/M (CI 95% [0.9 – 1.5]). Prevalence of syndromic forms  was estimated at 1.9/M (CI 95% [1.6 – 2.6]).Our results constitute a crucial basis to properly size the necessary health measures that are required to improve patient care and design further clinical studies. Inherited ichthyoses represent a large group of monogenic Mendelian disorders of cornification due to mutations in genes involved in skin barrier function . Skin chPlan Maladies Rares defined by the French Health ministry ). The probability of appearing in at least one list increased with disease severity: it was estimated that 95% of very severe patients (grade 4) were detected in the study vs. only half of mild patients (grade1).From this model, we also estimated the number of ichthyosis patients by age group Table : 58 patiad hoc approach).The estimated number of ichthyosis patients for each area is presented in Table The estimated regional prevalence of ichthyosis (95% CI) is presented in Table The diagnosis of the clinical form of ichthyosis was performed by the clinician in charge for 85.7% (102/119) of patients. For the remaining 17 patients , inclusion criteria were encountered  and the clinical form was unequivocally determined by the expert board. Estimated prevalence for each clinical form is presented in Table More than 85% of the patients had a non-syndromic form of ichthyosis, with two-thirds diagnosed as Autosomal Recessive Congenital Ichthyosis (ARCI). Prevalence of ARCI was estimated at 7/M (95% CI [5.7–9.2]) with a ratio Lamellar Ichthyosis (LI)/Congenital Ichthyosiform Erythroderma (CIE) of 2.4. When considering prevalence of ARCI by age group, the prevalence of patients under 15 years old and aged 15 and older were estimated at 12.1/M (95% CI [10.2 – 16.5] and 5.9/M (95% CI [4.5 – 8.7]), respectively. Prevalence of recessive X-linked Ichthyosis (XLI) was estimated to 2.4/M, i.e. 4.9 cases per million males (CI 95% [4.1 – 6.6]), according to a ratio female/male: 51.4%/48.6%, provided by the French 2008 census). Prevalence of keratinopathic forms was even lower: 1.1/M (95% CI [0.9–1.5]).Less than 15% of patients had syndromic ichthyosis with an estimated prevalence of 1.9/M (95% CI [1.6–2.6]). Netherton syndrome was the most frequent form, with 0.80/M (95% CI [0.66–1.06]).This is the first study investigating prevalence of inherited ichthyosis (excluding very mild forms) in France. This prevalence was estimated at 13.3/M , with more than half of the patients suffering from ARCI.Capture-recapture method was appropriate for estimating prevalence of rare diseases. Indeed, cross-sectional studies are the main alternative to estimate prevalence but may fail in case of rare disease because, even in large samples, it is possible to detect no case . Requirevia internet (more than 100 members). Recruitment via L2 and L3  was not negligible which confirmed the appropriateness of the capture-recapture method and the choice of the lists. The choice of the 5 areas was based on the presence of a reference/competence centre. These areas can be considered as representative of France since they are scattered throughout the country and cover more than 20% of the population.The choice of our 3 lists was based on the followings points: patients are often seen even once in expert centres for rare skin disease (L1). The association AIF (L2) is the only patient support group in France and registers a significant number of patients (approximately 250 members). The choice of a social network (L3) was based on patients’ enthusiasm for searching information or communicating ad hoc approaches. Other statistical approaches which require some specific theoretical developments are possible and could be proposed in future studies. To complete our statistical analysis, the pseudo-R2 proposed by Mc Fadden ) for the patients younger than 10 years. This age effect was also found in our estimates (23/M (95% CI [19–31]) for patients younger than 15 years old (12.1/M (95% CI [10.2 – 16.5]) when only considering ARCI). In the United States, incidence of ichthyosis during the first year of life (excluding common forms which are not diagnosed at birth) was estimated to 6.7 per 100.000 from large administrative claims databases ) which corresponds to a lower prevalence (0.44/M (CI 95% [0.28 – 0.59])) than ours. Nevertheless, Japanese patients seen only in Dermatology departments were concerned . With reThis is the first French epidemiological study on ichthyosis. It focused on ichthyoses with significant impact on QOL, usually followed in hospital and for which medical, social or research progresses are needed. The obtained results constitute an essential basis for properly sizing the necessary health measures such as access to molecular diagnosis or design of clinical studies, especially in the domain of therapeutics in which there is a true lack.The authors declare that they have no competing interest.ID designed and coordinated the study, contributed to collecting data, performed the revision and the interpretation of all the clinical data and wrote the manuscript. CC and JD co-designed the study, performed the statistical analyses and co-wrote the manuscript. SP participated in the statistical analyses. SH, CC, AM, LR, PV, LM, SM and SB contributed to collecting data. KE contributed towards collecting data and revising the manuscript. JMH designed and co-coordinated the study, contributed to the acquisition and interpretation of data and co-wrote the manuscript. All authors read and approved the final manuscript.


In this study, we interpreted the behavior of PM2.5 and its correlation with meteorological parameters in Hong Kong, during 2007–2008. Significant diurnal variations of PM2.5 concentrations were observed and showed a distinctive bimodal pattern with two marked peaks during the morning and evening rush hour times, due to dense traffic. The study observed higher PM2.5 concentrations in winter when the northerly and northeasterly winds bring pollutants from the Chinese mainland, whereas southerly monsoon winds from the sea bring fresh air to the city in summer. In addition, higher concentrations of PM2.5 were observed in rush hours on weekdays compared to weekends, suggesting the influence of anthropogenic activities on fine particulate levels, e.g., traffic-related local PM2.5 emissions. To understand the spatial pattern of PM2.5 concentrations in the context of the built-up environment of Hong Kong, we utilized MODerate Resolution Imaging Spectroradiometer (MODIS) Aerosol Optical Thickness (AOT) 500 m data and visibility data to derive aerosol extinction profile, then converted to aerosol and PM2.5 vertical profiles. A Geographic Information Systems (GIS) prototype was developed to integrate atmospheric PM2.5 vertical profiles with 3D GIS data. An example of the query function in GIS prototype is given. The resulting 3D database of PM2.5 concentrations provides crucial information to air quality regulators and decision makers to comply with air quality standards and in devising control strategies.Airborne fine particulates (PM Aerosol is defined as the total particles suspended in air with typical particle radius ranged from 0.05 to 15 μm [Airborne Particulate Matter (PM) refers to particles suspended in the air in either liquid or solid form, which are highly heterogeneous in both time and space and are often observable as dust, smoke and haze. PMto 15 μm . The scato 15 μm . Satelli2.5) can penetrate deeper into the air sacs of human lungs and therefore pose the greatest harm to human health [Airborne particulates can be inhaled by the human lungs, where they are absorbed into blood, and consequently are responsible for harmful health effects. The significance of adverse effects on our health depends on the size and composition of particulates. For instance, particles less than 2.5 μm , while the spatial patterns of PM2.5 will be derived from remote sensing and GIS approaches.Due to the temporal and spatial dependence of the pollutant, the characteristics of PMong Kong –19, theyong Kong . The ext2.2.1.2.5 concentrations in Hong Kong, the PM2.5 concentrations and meteorological data were acquired from the Hong Kong Environment Protection Department (HKEPD) and the Hong Kong Observatory (HKO) respectively. In this study, PM2.5 data recorded by Central station  equipped with a TEOM Series 1400a monitor [2.5 concentrations over urban areas in Hong Kong. These data are represented for the pollution in Central Business District and are considered to have higher values than suburban and rural areas. Temperature, relative humidity, pressure, and precipitation were collected from the HKO , which were used to represent the meteorological conditions for Central station  is a sensor aboard the TERRA and AQUA Earth observation system satellites. It is a multispectral , multi-resolution  sensor dedicated to the observation of the Earth. However the coarse spatial resolution (10 × 10 km) of MODIS Aerosol Optical Thickness (AOT), namely MOD04 aerosol product  cannot pet al. ,24 devel3.3.1.2.5 and meteorological parameters, the correlations between them were first calculated. The diurnal patterns of PM2.5 concentration and meteorological data were also studied to understand their influences during summer and winter time. In addition, seasonal variations of PM2.5 as well as meteorological parameters were studied. The daily concentrations (24 hour average) of PM2.5 and meteorological parameters of 2007 and 2008 were calculated from the hourly data and then grouped into each season such as spring (March–May), summer (June–August), autumn (September–November) and winter (December–February).In order to understand the interrelationship between PM3.2.2.5 measurement, satellite remote sensing provides aerosol optical thickness to study urban air pollution with broad spatial coverage [2.5 using linear regression models. Wang and Christopher [2.5 measured at seven locations in Alabama, United States. Wong et al. [2.5 (r2 = 0.67), which demonstrated great potential for MODIS derived 500 m AOT as a good surrogate for PM2.5 monitoring. In this study, we attempted to model the 2D (image) and vertical distributions of PM2.5 which has not been done in any other study. The resulting 3D database of PM2.5 concentrations can be used for daily air quality monitoring in environmental authority. First, the aerosol extinction profile (σa(z)) was modeled and the columnar AOT was divided into AOTΔz at different elevations [2.5 = 63.66 × AOT + 26.56) developed by Wong et al. [2.5Δz at different elevations can be derived.In contrast to ground level PMcoverage . AOT is coverage . Recent istopher  achievedg et al.  showed aevations ,30. Theng et al. , the PM21 and z2, AOTΔz between two elevations (Δz) can be computed [2 − z1):By integrating the extinction coefficient profile on two different elevations zcomputed  . It describes the decreasing rate of AOT with altitude and can be calculated using a(z0) can be derived from the visibility , and insignificances of the aerosol hygroscopic growth effect when relative humidity is less than 70% [Given the surface extinction coefficient σthan 70% ,36, the Δz by assigning any two given heights (Δz) in The whole columnar AOT can be divided to AOTz can be calculated from the extinction coefficient by inverting the Koschmeider equation  developed by Wong et al. [Finally, PMg et al. :(7)PM2.2.5Δz. Another program written in ArcEngine helps to display and visualize the data in 3D. The work flow of these programs is shown in A program code in Matlab has been developed for data matching and converting AOT to PM4.4.1.2.5 and meteorological parameters over Hong Kong on a daily average basis. Moderate correlations were observed between PM2.5 and temperature (TEMP), relative humidity (RH), and mean sea level pressure (MSLP), and fair correlations were observed from the other two parameters: wind speed (WS), wind direction (WD).4.2.2.5 and meteorological parameters. PM2.5 showed a distinctive diurnal pattern while low values observed during night time (01:00–05:00). During the daytime, PM2.5 exhibited a bimodal pattern with two marked peaks, during morning rush hours (08:00–10:00) and evening rush hours (18:00–20:00), typically when high traffic density occur. Similar observations and implications were reported by Chan and Kwok [and Kwok .2.5 in spite of the time lag, which displayed two clear maxima around 10:00 and 23:00. In contrast, temperature and wind speed exhibit a unimodal pattern characterized by midday maxima around 13:00. Relative humidity, however, exhibits an inverse unimodal pattern with stable overnight maximum values, which suggests the negative association with nocturnal PM2.5 concentrations. A high relative humidity can depress the absorption of gas phase organic species into particle surface [2.5 keeps constant at minimum values between 02:00 and 05:00. Another reason is due to less influence of anthropogenic activities on fine particulate levels during nighttime.Wind direction does not show a clear diurnal pattern. Mean sea level pressure has a similar pattern to that of PM surface  and acce surface . Thus, P2.5 concentrations is found to be lower than in winter. On the other hand, the peak values in Despite a similar pattern observed in 4.3.2.5 were obvious  prototype was developed in this study to integrate atmospheric PM2.5 vertical profiles with 3D GIS data which are provided by the Hong Kong Lands Department. This prototype utilized ESRI ArcGIS Scene Control component to present the landscape objects including the terrain model, building polygons, AOTΔz and PM2.5Δz grid data in 3D space. The functionality of this system provides scene rendering using perspective view. The 3D PM2.5Δz atmospheric layers corresponding to 500 m pixel columns were rendered using a transparent color scheme overlaid with the 3D building polygons. Since the system is aimed at the built environment within the city, only seven PM2.5Δz atmospheric layers, each has 75 m elevation, were created. In this GIS prototype, each building is corresponding with its cadastral footprint polygon, which owns attributes including building height, number of floors and height of each floor . The PM2.5Δz data can be related with each building by tabular linkage through the polygon-in-polygon function of the Hawths extension [2.5Δz concentrations and useful for direct query. The interface of this GIS prototype is shown in 2.5Δz concentrations of the International Commerce Centre on 1 February 2007 .In order to understand the spatial pattern of PMxtension . Therefo5.2.5, as well as its correlation with different meteorological parameters and the state-of-the-art technique for modeling and visualizing of atmospheric PM2.5Δz vertical profiles. In this study, the hourly based dataset, e.g., PM2.5 concentrations and five meteorological parameters e.g., wind direction, wind speed, temperature, relative humidity, and pressure were analyzed to explore their diurnal and seasonal variations and interrelations.The paper presents a comprehensive study of characteristics, behavior and trends of PM2.5 showed a distinctive bimodal pattern with two marked peaks: morning rush hours (08:00–10:00) and evening rush hours (18:00–20:00), which are mostly influenced by the dense traffic. The lower PM2.5 concentrations observed in summer than in winter may be caused by the wind direction. Northerly and northeasterly winds bring pollutants from the Chinese mainland in winter, whereas southerly monsoon winds from the sea bring fresh air to the city in summer. In addition, the higher concentrations of PM2.5 in rush hours on weekdays compared to those in weekends suggest the significance of anthropogenic activities e.g., traffic-related local PM2.5 emissions.PM2.5Δz values for different atmospheric heights were linked to a GIS-based 3D urban model to provide near-real time visualization. The resulting 3D database of PM2.5Δz concentrations provides crucial information to air quality regulators and decision makers to comply with air quality standards and in devising control strategies. This prototype will be integrated with web-interface system in the near future.The PM


It was reported that 35.5% of tuberculosis (TB) cases reported in 2003 in Taipei City had no recorded pre-treatment body weight and that among those who had, inconsistent dosing of anti-TB drugs was frequent. Taiwan Centers for Disease Control (CDC) have taken actions to strengthen dosing of anti-TB drugs among general practitioners. Prescribing practices of anti-TB drugs in Taipei City in 2007–2010 were investigated to assess whether interventions on dosing were effective.Lists of all notified culture positive TB cases in 2007–2010 were obtained from National TB Registry at Taiwan CDC. A medical audit of TB case management files was performed to collect pretreatment body weight and regimens prescribed at commencement of treatment. Dosages prescribed were compared with dosages recommended. The proportion of patients with recorded pre-treatment body weight was 64.5% in 2003, which increased to 96.5% in 2007–2010 (p<0.001). The proportion of patients treated with consistent dosing of a 3-drug fixed-dose combination (FDC) increased from 73.9% in 2003 to 87.7% in 2007–2010 (p<0.001), and that for 2-drug FDC from 76.0% to 86.1% (p = 0.024), for rifampicin (RMP) from 62.8% to 85.5% (p<0.001), and for isoniazid from 87.8% to 95.3% (p<0.001). In 2007–2010, among 2917 patients treated with either FDCs or RMP in single-drug preparation, the dosage of RMP was adequate (8–12 mg/kg) in 2571(88.1%) patients, too high in 282(9.7%), too low in 64(2.2%). In multinomial logistic regression models, factors significantly associated with adequate dosage of RMP were body weight and preparations of RMP. Patients weighting <40kg (relative risk ratio (rrr) 6010.5, 95% CI 781.1–46249.7) and patients weighting 40–49 kg  were more likely to receive higher-than-recommended dose of RMP.Prescribing practice in the treatment of TB in Taipei City has remarkably improved after health authorities implemented a series of interventions. Tuberculosis (TB) services were provided by general practitioners in Taiwan. TB was a notifiable disease by law. Completeness of TB notification in Taiwan has been investigated; 96.3% of patients who were prescribed 2 or more anti-TB drugs in 2005–2007 were notified to Taiwan Centers for Disease Control (CDC) Prescription of anti-TB drugs within national TB programme (NTP) routinely follows NTP manual and is usually more standardized than that among general practitioners. Studies conducted under programme conditions reported that the proportions of patients with recorded pre-treatment body weight were 73% in Kenya, 82% in Nepal, 98% in Senegal and 98% in Malawi Review of prescribing practices has been indicated as an essential tool for measuring the quality of TB services To assess whether these interventions on dosing were effective, a clinical audit was done to investigate prescribing practices of anti-TB drugs in Taipei City in 2007–2010. Primary objective was to assess whether there was difference between 2003 and 2007–2010 in prescribing practice of anti-TB drugs in Taipei City. Secondary objective was to investigate factors associated with inconsistent dosing of anti-TB drugs. We report results of this investigation.We tested the null hypothesis that interventions addressing inconsistent dosing were not effective and that there was no difference between 2003 and 2007–2010 in terms of the proportion of patients with recorded pretreatment body weight and the proportions of patients with consistent dosing of 3-drug FDC, 2-drug FDC, RMP, and INH. We extended the audit to ethambutol  and pyrazinamide  as well.Mycobacterium tuberculosis who were citizens of Taipei City reported to Taiwan CDC in the calendar year 2007–2010. Lists of all notified TB cases of Taipei City in 2007–2010 were obtained from National TB Registry at Taiwan CDC. Each TB case had a case management file maintained by public health nurses at Department of Disease Control and Prevention, Taipei City Department of Health. It contained information on history of TB, sputum examinations , body weight, prescription of anti-TB drugs (type of drugs and dosage), outcome of treatment, as well as age, sex, symptom profiles, family history of TB, concomitant diseases , smoking, use of alcohol beverage, and contact examinations. A structured questionnaire was designed for this audit and a team of 11 individuals were organized; the majority of them were senior nurses with substantial experience of TB services. The questionnaire was discussed, pilot tested, and revised for 4 times before it was finalized for data collection. A medical audit of TB case management files was performed in 2011 to collect pretreatment body weight and regimens prescribed at commencement of treatment. Dosages prescribed were compared with dosages recommended by Taiwan Guidelines for the diagnosis and treatment of TB The study population included all individuals with culture positive for Two types of FDC of anti-TB drugs were available in Taiwan, one containing three and the other two drugs. The three-drug tablet (Rifater) contains INH 80 mg, RMP 120 mg and PZA 250 mg (the ratios of H:R:Z were 1∶1.5∶3.1). The two-drug tablet was available in two different forms, one  containing INH 100 mg and RMP 150 mg (the ratio of H:R was 1∶1.5), and the other  with INH 150 mg and RMP 300 mg (the ratio of H:R was 1∶2). Concerning the 3-drug FDC, Taiwan CDC recommended 3 tablets per day for adults weighing <40 kg, 4 tablets for 40–49 kg and 5 tablets for ≥50 kg; and concerning the 2-drug FDC, 3 tablets of RFN150  for adults weighing <50 kg and 2 tablets of RFN300 per day  for adults weighing ≥50 kg.Taiwan CDC recommended 600 mg RMP for patients weighing ≥50 kg and 450 mg for those weighing <50 kg. The alternative recommendation is to prescribe 10 milligrams per kilograms (mg/kg) body weight (range 8–12 mg/kg) with 600 mg as the maximal dose.Taiwan CDC recommended 300 mg INH for the majority of patients and 200 mg for those with low body weight. Following the previous study, Taiwan CDC recommended 1500 mg PZA for patients weighing ≥50 kg and 1000 mg for those weighing <50 kg. The alternative recommendation is to prescribe 25 (range 20–30) mg/kg body weight with 2000 mg as the maximal dose.Taiwan CDC recommended 800 mg EMB for patients weighing 40–55 kg, 1200 mg for patients weighing 56–75 kg, and 1600mg for patients weighting 76–90 kg. The alternative recommendation is to prescribe 15 (range 15–20) mg/kg body weight.Dosages prescribed were further compared with internationally-recommend dosages in mg/kg body weight: 5 (4–6) mg/kg for INH, 10 (8–12) mg/kg for RMP, 15 (15–20) mg/kg for EMB and 25(20–30) mg/kg for PZA.P<0.05 was considered statistically significant. Relevant determinants were entered into multinomial logistic regression models in which the outcome variable had three categories: adequate dosage, lower-than-recommended dosage and higher-than-recommended dosage. Determinants remaining significant in the multinomial logistic regression models were retained and a final fitted model was determined by backward elimination using the likelihood ratio test.To ensure accuracy of data entry, the complete data set was double entered separately by 2 team members, and validated using EpiData Entry 3.1 . Discrepant records were checked and corrected against the original data on the questionnaires. STATA Version 12  was used for statistical analysis. Categorical variables were analysed using Pearson's χ2 test. The study was approved by the Taiwan CDC review board and was funded by the Taiwan CDC. The study reviewed routine surveillance data recorded on national TB registry and TB case management files and did not involve any human participation. Therefore, the project was not considered to require review by an ethics committee and informed consent was waived.A total of 6790 TB cases were notified to Taipei health authorities and Taiwan CDC in 2007–2010.  Of the 3Of the 2990 patients, 2627(87.9%) were prescribed HRZE, 209(7.0%) HRE, 89 (3.0%) HRZ, and 65 (2.2%) other regimens. Of the 2990 patients, 2917(97.6%) were treated with RMP containing regimens, in which 1849(63.4%) were treated with a 3-drug FDC, 514(17.6%) a 2-drug FDC, and 553(19.0%) RMP.Among the 1849 patients treated with a 3-drug FDC (Rifater), the dosage was consistent with Taiwan guidelines in 1622(87.7%), too high in 162(8.8%), too low in 65(3.5%). Of the 514 patients treated with 2-drug FDCs, 125 were treated with RFN150, 384 with RFN300, and 5 patients with both RFN150 and RFN300. Among the 125 patients treated with RFN150, the dosage was consistent in 91(72.8%) patients, too high in 15(12.0%), and too low in 19(15.2%). The proportion of patients treated with too low a dosage of RFN150 was 27.8% in 2007, which decreased to 12.5% in 2010 (p = 0.138). Among the 384 patients treated with RFN300, the dosages were consistent with Taiwan guidelines in 347(90.4%), too high in 36(9.4%), and too low in 1(0.3%). The proportion of patients treated with too low a dosage of RFN300 was 1.4% in 2007, which decreased to 0 in 2010 (p = 0.455).Due to unbalance ratios of H:R:Z in Rifater and of H:R in RFN150, the dosage of INH in mg/kg body weight was too high in 99.4% of patients treated with Rifater  and in 8Among the 553 patients treated with RMP, the dosage was consistent with Taiwan guidelines in 473(85.5%), too high in 51(9.2%), too low in 29(5.2%). The proportion of patients treated with too low a dosage of RMP was 10.5% in 2007, which decreased to 0.9% in 2010 (P = 0.007). ApplyingA total of 590 patients were treated with INH. Applying the Taiwan guidelines' recommendation of 300 mg of INH for most patients and 200 mg for those weighing ≤40 kg, the dosage of INH was consistent in 562(95.3%), too high in 20(3.4%), and too low in 8(1.4%). ApplyingA total of 825 patients were treated with PZA. Applying the Taiwan guidelines' recommendation, the dosage of PZA was adequate in 650(78.8%), too high in 71(8.6%), too low in 104(12.6%). The proportion of patients receiving too low a dosage of PZA was 19.8% in 2007, which decreased to 12.4% in 2010 (P = 0.001).  ApplyingOverall, among 2917patients treated with either Rifater, or Rifinah, or RMP in single-drug preparation, the dosage of RMP was adequate (8–12 mg/kg) in 2571(88.1%) patients, too high in 282(9.7%), too low in 64(2.2%). In multinomial logistic regression models, factors significantly associated with adequate dosage of RMP were body weight and preparations of RMP.  PatientsOverall, among 2954 patients treated with either Rifater, or Rifinah, or INH in single-drug preparation, the dosage of INH was adequate (4–6 mg/kg) in 783(26.5%), too high in 2155(73.0%), too low in 16(0.5%). In multinomial logistic regression models, factors significantly associated with adequate dosage of INH were body weight and preparations of INH.  PatientsOverall, among 2674 patients treated with either Rifater or PZA, the dosage of PZA is adequate (20–30 mg/kg) in 1974(73.8%) patients, too high in 88(3.3%), too low in 612(22.9%). In multinomial logistic regression models, factors significantly associated with adequate dosage of PZA were sex, body weight and preparations of PZA.  Male , too high for 125(4.4%), too low for 1141(40.2%).  ApplyingIn summary, the proportion of patients with recorded pre-treatment body weight was 64.5% in 2003, which increased to 96.5% in 2007–2010 (p<0.001). The proportion of patients treated with consistent dosing of Rifater increased from 73.9% in 2003 to 87.7% in 2007–2010 (p<0.001), and that for Rifinah from 76.0% to 86.1% (p = 0.024), for RMP from 62.8% to 85.5% (p<0.001), and for INH from 87.8% to 95.3% (p<0.001).The study showed that it was possible to strength prescribing practice in the treatment of TB among general practitioners. The proportion of TB patients notified in Taipei City who did not have recorded pretreatment body reduced to none in 2010. The proportion of patients treated with consistent dosages of anti-TB drugs increased substantially and the proportion of patients treated with lower-than-recommended dosage reduced drastically. This was remarkable as it was usually difficult to involve general practitioners in TB services Prescribing practices of PZA and EMB were less satisfactory, especially EMB, partly because prescribing practicing of PZA and EMB was not analyzed in 2003, partly because the role of EMB in the treatment of TB was not as prominent as RMP and INH. Many practitioners in Taiwan were not used to prescribe more than 800 mg EMB, due to the concern of adverse drug effect of EMB. The impact of inadequate dosing of EMB related to outcome of treatment and generation of drug resistance need further evaluation.Although prescribing practice has been more consistent with Taiwan guidelines, the preparation of Rifater available in Taiwan had unbalance ratios of INH, RMP and PZA (1∶1.5∶3.1), and RFN150 had an unbalance ratio of INH and RMP (1∶1.5). As a result, dosing of RMP in an adequate range resulted in higher-than-recommended doses of INH in patients treated with Rifater and RFN150, and lower-than-recommended doses of PZA in patients treated with Rifater. This was not the case of RFN300 as the ratio of INH and RMP in each tablet of RFN300 was 1∶2, which is consistent with the ratio of recommended dosages of INH and RMP in mg/kg body weight. To avoid over-dosing of INH and under-dosing of PZA, the preparations of FDCs must be modified Body weight was another important factor that was significantly associated with inadequate dosing of anti-TB drugs In conclusion, prescribing practice in the treatment of TB in Taipei City has remarkably improved after health authorities implemented a series of interventions. To have further improvement on dosing of anti-TB drugs, inadequate preparation of FDCs needs to be addressed and prescribing practice of EMB needs additional attention. Other settings where prescribing practice of anti-TB drugs have not yet been assessed should be encouraged to conduct similar clinic audits.