The international WAO/EAACI guideline for the management of hereditary angioedema-The 2017 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: (1) How should HAE-1/2 be defined and classified?, (2) How should HAE-1/2 be diagnosed?, (3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, (4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and (5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures?

Challenges of C1-inhibitor concentrate self-administration.

Self-administration of therapy can help hereditary angioedema (HAE) patients regain control of their disease or reduce its impact and improve the quality of their lives. However, data from a self-administration survey, and subsequent discussion at an international HAE expert meeting, identified several barriers to self-administration therapy. These barriers include difficulty in administration technique, availability of nursing resources and the mental capacity of the patient. Encouragingly, international HAE experts identified that once a patient has acquired self-administration skills, they generally retain them in the long-term. As patient uptake increases, it was recommended that follow-up management plans should be established to address any issues from the patient's perspective.

Structure and oxygen mobility in mayenite (Ca12Al14O33): a high-temperature neutron powder diffraction study.

The structure of mayenite, Ca(12)Al(14)O(33), was investigated by neutron powder diffraction up to 1323 K. It has been described previously as a calcium-aluminate framework, in which 32 of the 33 oxygen anions are tightly bound, containing large cages, 1/6 of them being filled randomly by the remaining 'free' oxygen. At ambient temperature excess oxygen was found, corresponding to the composition Ca(12)Al(14)O(33.5) which was attributed to the presence of hydroxide, peroxide and superoxide radicals in the cages. Above 973 K these are lost under vacuum conditions and the composition becomes stoichiometric. From the refined structural parameters it is concluded that the structure is more adequately described as a relatively stable aluminate framework consisting of eightfold rings of AlO(4) tetrahedra with disordered Ca and 'free' O distributed within. At high temperatures the density of the 'free' oxygen is extremely spread out, with the expansion being related to the high ionic conductivity of this material. Since no continuous density distribution between adjacent cages was found and the 'free' O forms bonds with part of the Ca, the diffusion proceeds via a jump-like process involving exchange of the 'free' oxygen with framework oxygen. The results confirm the recent theoretical predictions of Sushko et al.

One-dimensional scattering in K-hollandite: theory and experiment.

This work comprises calculations using the Frenkel-Kontorova and double-chain models, which led to new results explaining the experimental diffraction pattern of K-hollandite. The use of a deformable host chain and a Lennard-Jones-like interchain interaction gives the best results. From these calculations, it can also be concluded that the guest as well as the host are deformed and that the system is pinned. The inclusion of Debye-Waller factors as fitting parameters is also discussed, with the conclusion they should not be used in the case of the double-chain model.

The natural history of periodontal disease in man. Risk factors for progression of attachment loss in individuals receiving no oral health care.

BACKGROUND: Few investigations have reported on risk factors for periodontal attachment loss over time in subjects with no home or professional dental care. The purpose of this report was to identify potential risk factors for progression of periodontal attachment loss among male Sri Lankan tea laborers who participated in a 20-year investigation of the natural history of periodontal disease. METHODS: Data for this report were obtained from the 154 subjects who participated in the 1970 baseline and the final 1990 examinations and included data from their interim examinations performed in 1971, 1973, 1977, 1982, and 1985. Oral health assessments included: 1) attachment levels in millimeters on mesial and mesio-buccal surfaces of all but third molar teeth; 2) plaque index (PI); 3) gingival index (GI); 4) calculus index (CI); 5) caries index (DMFS); and 6) presence or absence of teeth. Other variables included age, history of smoking, and/or use of betel nut. Statistical analyses used multivariate repeated measures analysis of variance (ANOVA). RESULTS: The final adjusted model indicated that attachment loss increased significantly with age (X2 = 74.0; df = 1), GI (X2 = 45.5; df = 1), CI (X2 = 52.7; df = 1) and follow-up time (X2 = 219.8; df = 6, P<0.0001 for all variables). CONCLUSIONS: Age, GI, CI, and time were significantly associated with mean attachment loss over 20 years. Neither PI, history of smoking, or history of betel nut use were significantly associated with attachment loss over time.

The influence of margins of restorations of the periodontal tissues over 26 years.

AIM: The purpose of this investigation was to examine the long-term relationship between dental restorations and periodontal health. MATERIAL AND METHODS: The data derived from a 26-year longitudinal study of a group of Scandinavian middle-class males characterized by good to moderate oral hygiene and regular dental check-ups. At each of 7 examinations between 1969 and 1995, the mesial and buccal surfaces were scored for dental, restorative and periodontal parameters. The mesial sites of premolars and molars of 160 participants were observed during 26 years (1969-1995). A control group with 615 sound surfaces or filling margins located more than 1 mm from the gingival margin in all 7 surveys was compared with a test cohort with 98 surfaces which were sound or had filling margins located more than 1 mm from the gingival margin at baseline (1969) and had a subgingival filling margin 2 years after (1971). RESULTS AND CONCLUSIONS: The study confirmed the long held concept that restorations placed below the gingival margin are detrimental to gingival and periodontal health. In addition, this study suggests that the increased loss of attachment found in teeth with subgingival restorations started slowly and could be detected clinically 1 to 3 years after the fabrication and placement of the restorations. A subsequent "burn-out" effect was suggested.

Longitudinal positional ordering of n-alkane molecules in urea inclusion compounds

The profiles of diffuse layers, which are present in diffraction patterns of urea inclusion compounds, are interpreted quantitatively by a longitudinal positional paracrystalline order of the alkane guest molecules within the channels of the urea-host framework structure, in agreement with the expected behaviour of a one-dimensional system. With decreasing temperature there is a gradual transition into long-range order behaviour. This ordering process remains unaffected by structural changes related to lateral correlations within and between both host and guest substructures, including a structural phase transformation. The differing behaviour of a mixed system (pentadecane/hexadecane) with average period almost commensurate with the urea host lattice is explained by the superposition of main and satellite layers. The distribution of both molecules within each tunnel is random.

The informativeness of attachment loss on tooth mortality.

BACKGROUND: In periodontal clinical trials, clinical attachment level measurements are commonly used as surrogates for tooth loss. Conclusions regarding treatment efficacy in these trials are valid if: 1) the surrogate is informative on tooth loss, and 2) the surrogate captures the effect of treatment on tooth loss. The goal of this study was to evaluate the first criterion: Are serial clinical attachment loss measurements informative on overall tooth mortality? METHODS: Young Norwegian men (aged 17 to 35) were first examined in 1969 (n=565) and followed for 26 years with examinations in 1971 (n=381), 1973 (n=292), 1975 (n=245), 1981 (n=228), 1988 (n=202), and 1995 (n=223). Several aspects of the serial attachment loss measurements were related to tooth mortality risk using statistical models that take into account the time-dependent changes of the clinical attachment loss measurements. RESULTS: The results provided evidence that moderate attachment losses were informative on tooth mortality. Both the lifetime cumulative attachment loss, as well as attachment loss since young adulthood, of > or = 2 mm or > or = 3 mm was informative on tooth mortality. Tooth mortality risk increased as the attachment loss increased; loss > or = 3 mm at the buccal or mesial site increased tooth mortality risk, by 91% (relative risk, 1.91; 95% confidence interval, 1.01-3.60) and 270% (RR, 3.70; 95% CI, 1.83-7.49), respectively. CONCLUSIONS: We concluded that clinical attachment loss was moderately informative on overall tooth mortality in this Norwegian population. Since this finding has now been demonstrated in 3 different populations, the focus of further research should be on evaluating whether the second criterion for a valid surrogate is satisfied: Does clinical attachment loss capture the effect of periodontal treatments on tooth loss?

Forty-five-year tooth survival probabilities among men in Oslo, Norway.

Changes in tooth survival probabilities over a person's lifetime have remained largely unexplored. The goal of this study was to evaluate changes in the 45-year tooth survival probabilities in a cohort of 565 Norwegian males who were examined in 1969 as young adults, and followed up into mid-life (examination years and sample sizes (n): 1971 (n = 381), 1973 (n = 292), 1975 (n = 245), 1981 (n = 228), 1988 (n = 202), and 1995 (n = 223). The results indicated that the tooth survival probabilities varied considerably both (i) among teeth within individuals, and (ii) over time. The 45-year survival probabilities for the 28 teeth fell into the following ranges: larger than 95% for incisors and cuspids; between 84% and 92% for premolars; and between 59% and 96% for molars. Over the first 4 post-eruptive decades, the tooth mortality risks (excluding orthodontic extractions) were: 1st decade, 2.0% (from 1.7 to 2.4%); 2nd decade, 0.2% (from 0.1 to 0.4%); 3rd decade, 0.6% (from 0.4 to 0.8%); and 4th decade, 1.1% (from 0.8 to 1.5%). The tooth mortality risks in the 2nd, 3rd, and 4th decades were probably somewhat underestimated (due to dropout bias), suggesting that the true underlying tooth mortality hazard function may have been V-shaped. The conclusions were that the tooth mortality hazard during the first 4 post-eruptive decades was bathtub-shaped and that it varied considerably among teeth within individuals.

The natural history of periodontal disease. The correlation of selected microbiological parameters with disease severity in Sri Lankan tea workers.

The purpose of this study was to assess the prevalence of A. actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia, and their association with periodontal disease states in a population sample from Sri Lanka. Based on clinical parameters, a total of 536 sites in 268 male Sri Lankan tea workers were categorized as healthy, or showing gingivitis only, moderate or advanced periodontitis. Bacterial samples were obtained from all sites and the three target bacteria identified by indirect immunofluorescence. P. intermedia, P. gingivalis and A. actinomycetemcomitans were found in 76%, 40% and 15% of the subjects, respectively. Of the 536 periodontal sites, 10.5% were categorized with "no disease", 14% "gingivitis only": 59% with moderate and 16% with advanced periodontitis. The prevalence of P. gingivalis and P. intermedia was significantly higher in sites with moderate and advanced periodontitis than in sites with no disease or gingivitis only. A. actinomycetemcomitans was not found in healthy sites, but occurred with equal frequency in sites with gingivitis, moderate and advanced periodontitis. The association between these three bacteria and periodontal diseases in Sri Lankan tea laborers was similar to that described for other non-industrialized and industrialized countries.

The natural history of periodontal disease in man: prevalence, severity, and extent of gingival recession.

This paper describes the occurrence and levels of gingival recession in 2 cohorts of individuals participating in parallel longitudinal studies in Norway (1969-1988) and Sri Lanka (1970-1990), covering the age range from 15 to 50 years. In the Norwegian cohort gingival recession had begun early in life. It occurred in greater than or equal to 60% of the 20 year-olds and was confined to the buccal surfaces. At 30, greater than or equal to 70% had recession, which still was found mainly on buccal surfaces. As the group approached 50 years of age, more than 90% had gingival recession; greater than or equal to 25% of the buccal surfaces were involved, greater than or equal to 15% of lingual, and 3 to 4% of the interproximal surfaces. In the Sri Lankan cohort greater than or equal to 30% exhibited gingival recession before the age of 20 years. By 30 years, 90% had recession on buccal, lingual, and interproximal surfaces; and at 40 years, 100% of the Sri Lankans had recession. As they approached 50 years, gingival recession occurred in greater than or equal to 70% of the buccal, greater than or equal to 50% of the lingual, and 40% of the interproximal surfaces. Based on the special features of the two cohorts, the working hypothesis is advanced that there is more than one type of gingival recession and probably several factors determining the initiation and development of these lesions.

Inositol tetrakisphosphates as second messengers induce Ca(++)-dependent chloride currents in Xenopus laevis oocytes.

Microinjection of inositol 1,3,4,5-tetrakisphosphate or inositol 1,4,5-trisphosphate induced distinct chloride membrane currents in defolliculated Xenopus laevis oocytes. To decide whether these Cl(-)-currents were due to the injected compounds or their metabolic products, [3H]Ins(1,3,4,5)P4 or [3H]Ins(1,4,5)P3 were injected into oocytes and their metabolites were analyzed by HPLC. Our results indicate that Ins(1,3,4,5)P4 itself or its metabolite Ins(1,3,4,6)P4 is able to induce Cl(-)-membrane currents, most likely by increasing the cytosolic Ca(++)-concentration.

Errors in measuring parameters associated with periodontal health and disease.

The intra-examiner reliability for the Plaque Index (PII), Calculus Index (CI), Gingival Index (GI), and periodontal loss of attachment (LA) was evaluated in 2 different physical and clinical environments. Examiner reliability for each index was consistently better when clinical evaluations were performed in an office setting on subjects who had low levels of periodontal disease than under more difficult field conditions evaluating subjects with higher disease levels. In an office environment intra-examiner reliabilities were very good for subject-based averages (intraclass r's were 0.85, 0.83, 0.81, and 0.78 for GI, PII, LA, and CI, respectively); they were moderate to good for site-based scores (kappas were 0.63, 0.54, and 0.47 for CI, GI, and PII). Under field conditions reliabilities ranged from excellent to fair for subject-based averages (intraclass r's of 0.98, 0.86, 0.76, and 0.33 for LA, CI, GI, and PII, respectively); for site-based scores they ranged from moderate to fair (kappas of 0.50, 0.49, and 0.21 for GI, CI, and PII, respectively). Small but significant systematic errors were detected under field conditions for the PII and CI, and for the PII in the office environment as well. The results observed suggest that the examination process can affect the clinical status of the surface or site when replicate assessments of plaque and calculus are conducted within a 24-hour period. Our results also confirm that measurement error standard deviation for loss of attachment evaluated with a periodontal probe can be maintained at 0.13 mm for whole-mouth means and 0.54 mm for individual sites, even when examining subjects with substantial periodontal disease under field conditions.

The natural history and clinical course of calculus formation in man.

This paper describes levels and progression of supra- and subgingival calculus undisturbed by active professional intervention or home care between 1970 and 1985 in Sri Lanka, or when removed at regular intervals between 1969 and 1988 in Norway. In the Sri Lankan tea laborers, both supra- and subgingival calculus formation started before age 14 years. At 40 years of age, all participants and almost all teeth and tooth surfaces had calculus. Tea laborers who both smoked tobacco and chewed betel had significantly higher calculus scores than those who only had one of these habits, and those who neither chewed nor smoked had the lowest calculus scores. Teeth with calculus showed a significantly higher rate of loss of attachment than teeth that remained calculus free. For the Norwegians who had enjoyed regular dental care throughout their lives, supragingival calculus did not increase in frequency from adolescence to the forties. Approximately 70% of the interproximal surfaces were calculus free after 40-50 years of age. Subgingival calculus scores, although low, showed some increase with longer times of exposure. On average, each person had 0.4 interproximal surfaces with subgingival calculus as they approached 50 years of age. In this Norwegian population, subgingival calculus had no impact on loss of attachment.

Natural history of periodontal disease in man. Rapid, moderate and no loss of attachment in Sri Lankan laborers 14 to 46 years of age.

This paper describes the initiation, rate of progress of periodontal disease and consequent tooth loss in a population never exposed to any programs or incidents relative to prevention and treatment of dental diseases. The group consisted of 480 male laborers at two tea plantations in Sri Lanka. The study design and baseline data have been published. At the initial examination in 1970, the age of the participants ranged between 14 and 31 years. Subsequent examinations occurred in 1971, 1973, 1977, 1982 and 1985. Thus, the study covers the age range 14-46 years. Throughout the study, the clinical indices were scored by the same two examiners, both well-trained and experienced periodontitis. Intra-examiner reproducibility for each index was tested at baseline and repeated periodically during the study. The data for each examination were computerized and updated on an ongoing basis. At the last examination in 1985, there were 161 individuals who had participated in the first survey. This population did not perform any conventional oral hygiene measures and consequently displayed quite uniformly large aggregates of plaque, calculus and stain on their teeth. Virtually all gingival units exhibited inflammation. Based on interproximal loss of attachment and tooth mortality rates, three subpopulations were identified: (1) individuals (approximately 8%) with rapid progression of periodontal disease (RP), those (approximately 81%) with moderate progression (MP), and a group (approximately 11%) who exhibited no progression (NP) of periodontal disease beyond gingivitis. At 35 years of age, the mean loss of attachment in the RP group was approximately 9 mm, the MP group had approximately 4 mm and the NP group had less than 1 mm loss of attachment. At the age of 45 years, the mean loss of attachment in the RP group was approximately 13 mm and the MP group approximately 7 mm. The annual rate of destruction in the RP group varied between 0.1 and 1.0 mm, in the MP group between 0.05 and 0.5 mm, and in the NP group between 0.05 and 0.09 mm. Since this population was virtually caries free, essentially all missing teeth were lost due to periodontal disease. In the RP group, tooth loss already occurred at 20 years of age and increased throughout the next 25 years. At 35 years of age, 12 teeth had been lost, at 40 years of age 20 teeth were missing and at 45 all teeth were lost. In the MP groups, tooth mortality started after 30 years of age and increased throughout the decade.(ABSTRACT TRUNCATED AT 400 WORDS)

The use of six selected teeth in population measures of periodontal status.

Selected teeth have been used to represent the entire dentition in many epidemiological and clinical investigations. The present study sought to assess the relationship between the six selected teeth described by Ramfjord and the entire dentition for the Plaque Index, Gingival Index, Calculus Index and Loss of Attachment. The computations were performed on measurements obtained in investigations of the natural history of periodontal disease in Norway and Sri Lanka. A consistently strong correlation was observed between the tooth subset and whole mouth for all indices in both populations. This relationship persisted even though single members or pairs of the subset of teeth were removed from the calculations. Some bias, however, was observed with all indices. Plaque and gingival indices obtained from the six teeth underestimated whole mouth scores in the low range (less than 1.0) and overestimated scores in the high range (greater than 2.0). Use of the tooth subset for calculus and loss of attachment consistently overestimated scores for the entire dentition.