Prevalence, incidence and outcome of periodontal diseases among the elderly

When compared to adults, older persons have a higher prevalence and incidence of periodontal diseases. The prevalence of periodontitis is substantially greater in the geriatrics group, which is 75 years old on average, compared to those who are 60 years old on average. Periodontitis can lead to tooth loss if natural periodontal therapies are not used. Periodontitis is the sixth most frequent incurable illness in the world, characterized by bacterial-induced and host-mediated deterioration of both soft and hard structures around the teeth. A severe type of periodontitis affects around 10% of the world's population. Periodontitis is more frequent in adults because of its chronic and debilitating nature, with around 66% of the 65-year-old age group in the United States afflicted by chronic periodontitis. A critical component of a successful disease prevention and health promotion trajectory is having up-to-date information on demographics, clinical symptoms, and illness burden on individuals, particularly in underrepresented regions where preventive programs are targeted and executed. As a result, the purpose of this paper is to evaluate the existing research on the prevalence, incidence, and consequences of periodontal diseases in the older population.

Estimation of C* Integral for Mismatched Welded Compact Tension Specimen

The C* integral for the compact tension (CT) specimen is calculated using the estimation equation in ASTM E1457-15. This equation was developed based on the assumption of material homogeneity and is not applicable to a welded CT specimen. In this paper, a modified equation for estimating the C* integral for a welded compact tension (CT) specimen under creep conditions is proposed. The proposed equation is defined on the basis of systematically conducted extensive finite element (FE) analyses using the ABAQUS program. A crack in the welded CT specimen is located in the center of the heat-affected zone (HAZ), because the most severe type IV cracks are located in the HAZ. The results obtained by the analysis show that the equation for estimating the C* integral in ASTM E1457-15 can underestimate the value of the C* integral for creep-soft HAZ and overestimate for creep-hard HAZ. Therefore, the proposed modified equation is suitable for describing the creep crack growth (CCG) of welded specimens.

AN AYURVEDIC CASE REPORT ON AMYOTROPHIC LATERAL SCLEROSIS

Amyotrophic Lateral Sclerosis (ALS) is a common and most severe type of Motor Neuron Disease. It is characterized by progressive skeletal muscle weakness, wasting and fasciculations. Survival is for 3-5 years, and the death is from respiratory paralysis. The incidence of ALS is between 0.6 and 3.8 per 100000 persons per year. Males are predominantly affected. Here is a case report of 45yrs old male who presented with complaints of difficulty in walking since 3years, with an insidious asymmetric onset of weakness of bilateral lower limbs with wasting and fasciculations. In Ayurveda, the case was symptomatologically diagnosed as Mamsa Sosha, which occurs as the result of obstruction of Snayu and Rakthadhamanis (Mamsavaha srotomoolas). The assessment was done using ALSFRS-R Scale. The treatment was aimed at improving the quality of life and also decreasing the rate of disease progression. The treatment principle adopted was Srothosodhana (Ama- Avaranaghna cikitsa) and Brimhana. Promising results were obtained after treatment. Keywords: ALS, MND, Ayurveda, Avaranaghna cikitsa, Mamsa Sosha, Mamsa Kshaya

Clinical Predictors and Prediction Models for Frequency of Total and Joint Hemorrhage in Severe-Type Patients with Hemophilia a (PwHA) with/without Intermediate-Dose Prophylaxis Therapy with rFVIII

Introduction: It was well-known that severe-type patients with hemophilia A (PwHA) had great variability in bleeding phenotypes. Factors effecting bleeding patterns of PwHA include at least treatment modality and interindividual various procoagulant and anticoagulant levels. We aimed to investigate what clinical variables could predict bleeding frequency of severe PwHA and to develop models for predicting bleeding phenotypes among severe PwHA with/without FVIII prophylaxis therapy. Methods and materials: Totally 51 severe-type previously-treated PwHA from two Hemophilia Centers in Taiwan were enrolled, who received standard half life (SHL) rFVIII products with complete consecutive bleeding records at least more than 6 months, and their medical charts 2017－2018 were retrospectively viewed. The clinical data were collected for analysis, including age, body mass index (BMI), body weight (BW), ABO blood groups, hemoglobin (Hb), hematocrit (Hct), HCV infecton, HIV infection, treatment modality, baseline VWF levels, and genetic defects. Baseline VWF activity meant the data via VWF:ACL activity or VWF:RCo. Clinical variables for annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) were evaluated by multivariate linear regression (MVLR) analysis. Results: The cohort of 51 severe-type PwHA included 8 boys and 43 adults, aged 8-64. For treatment modality, there were 19 patients receiving episodic treatment (ET) and 32 receiving prophylaxis therapy (PT) with intermediate-dose standard half life (SHL) rFVIII. The mean study period was 11.9 months, range 10－14.5 months. Among them, there were 31 with HCV infection and 4 with HIV infection. PwHA with non-O blood group were 31 and those with O blood group 20. The mean baseline VWF:Ag was 115.6±55.5%, range 50%－294.7%. The mean baseline VWF:activity was 105.4±52.1%, range 41.3%－307%. ABR of ET group and PT group were 46.1±29.2 and 6.8±7.1, respectively. (p<0.0001***) AJBR of ET group and PT group were 37.3±27.7 and 6.0±6.8, respectively. (p=0.0001***) By MVLR analysis, both treatment modality and baseline VWF:Ag were recognized as inverse predictors of ABR and AJBR, and HCV infection recognized a predictor for AJBR. Age, inhibitor histroy, BMI, BW, ABO blood groups, Hct, Hb, HIV infection, and missense mutation or not were eliminated as predictors. The predictive equations by MVLR were as the following two: (1) Predictive ABR = 56.5 - 37.8 * (Treatment model) - 11.8 * baseline VWF:Ag (IU/mL). (2) Predictive e AJBR = 41.9 - 28.6 * (Treatment model) - 12.0 * baseline VWF:Ag (IU/mL) + 10.0 * (HCV infection). (1 if Treatment model is PT, 0 if Treatment model is ET. 1 if HCV infection or anti-HCV antibody is positive, 0 if HCV infection or HCV antibody is negative.) Separate prediction models developed from MVLR analysis could explain 52.51% of the ABR variability and 50.56% of the AJBR variability. The correlation between predicted and observed bleeding frequency was significantly strong.(P-rank>0.7, p-value<0.0001***) Mean difference between predicted ABRs and observed ABRs was 1.75 and that between predicted AJBRs and observed AJBRs was 1.27. Predicted ABR deviated <21 (<2 per month) of observed ABR in 42/50 patients (84%). Predicted AJBR deviated < 24 (<2 per month) ofobserved AJBR in 44/50 patients (88%). Conclusion: Prophylaxis therapy and baseline VWF:Ag levels were the strongest two inverse predictors for ABR and AJBR. Positive HCV infection was another predictor for AJBR. The prediction models provided with an insight into personal bleeding quantified patterns and may identify PwHA with high bleeding risks based on individual characteristics of treatment modality, baseline VWF:Ag, and HCV infection. Our approach is of help for individualized treatment and refining of dosing strategies. Disclosures No relevant conflicts of interest to declare.

Meta-Analysis of D-Dimer, hsCRP and Cytokines in COVID-19 Severe/Critical Patients in China

Objective: To analyze the relationship between D-dimer, inflammatory markers, cytokines and disease severity, and the possibility of early identification of COVID-19 critical type patients. Methods: PubMed, EMBASE and CNKI databases were searched by computer, and references of related reviews and systematic reviews were manually searched as supplements. The retrieval deadline is February 9, 2021. According to the inclusion and exclusion criteria, the literatures were screened and the quality was evaluated, and then the data were extracted for meta-analysis. The fixed/random effects model was used to calculate the weighted mean difference (WMD) and 95% CI to evaluate whether the levels of D-dimer, hsCRP, IL-6, IL-8, IL-10 and TNF-α in critical type patients were statistically different from those in severe type patients. If there were statistical differences, logistic regression analysis was used, and establish the receiver operating characteristic curve (ROC) and area under the curve (AUC) of each index for the diagnosis of critical type patients. The best diagnostic value of COVID-19 critical type patients was calculated by Youden index. Results: A total of 3519 literatures entered the screening process. According to the inclusion and exclusion criteria, 40 articles were finally included in this study, and all of them were high-quality studies after evaluation. The results of meta-analysis showed that the levels of D-dimer, hsCRP, IL-6, IL-8 and IL-10 in critical type group were significantly higher than those in severe type group (P<0.05). Based on ROC curve, the AUC of D-dimer was 0.785 (95% CI: 0.671-0.899), AUC of hsCRP was 0.884 (95% CI: 0.632-1.000), AUC of IL-6 was 0.819 (95% CI: 0.700-0.939), which had diagnostic significance for critical type patients (P<0.05). The optimal diagnostic threshold of D-dimer was ≥2.00 mg/L (sensitivity 89.3%, specificity 64.0%); the optimal diagnostic threshold of hsCRP was ≥64.22 mg/L (sensitivity 75.0%, specificity 100%); the optimal diagnostic threshold of IL-6 was ≥33.01 ng/L (sensitivity 68.0%, specificity 92.0%). Conclusion: The levels of D-dimer, hsCRP, IL-6, IL-8 and IL-10 in COVID-19 critical type patients were significantly higher than those in severe type patients. Our results might be helpful in identify and risk reduction of mortality in critical types patients infected with COVID-19. Disclosures No relevant conflicts of interest to declare.

Real-World Bleeding Outcomes, Weekly Factor Consumption Doses, Annualized Factor Costs in Severe-Type Patients with Hemophilia a (PwHA) before and after Switching to Extended Half-Life rFVIII-Fc Prophylaxis

Introduction: Stand half-life (SHL) rFVIII had been used in patients with hemophilia A (PwHA) for episodic treatment (ET) and prophylaxis therapy (PT) for years. Extended half-life (EHL) rFVIII had been available since 2014, also available in Taiwan since 2018, and resulted in markedly increased willingness for PT because it reduced injection burden. We aimed to investigate the real-world bleeding outcomes, weekly factor doses, and factor costs of severe-type PwHA with pre-switch SHL rFVIII and post-switch EHL rFVIIIFc prophylaxis in Taiwan, and made a pre-switch and post-switch comparison. Methods and Materials: There were totally 51 non-inhibitor, severe-type PwHA, with complete bleeding records before and after switching from SHL rFVIII to EHL rFVIII-Fc, enrolled from two hemophilia centers during Nov, 2018－July, 2019. Most of them had various degree of one to more major joints arthropathy, except children. The medical charts were retrospective reviewed and data were collected, including body features and factor regimen, etc. Patients' annualized bleeding/joint-bleeding rate (ABR/AJBR), weekly doses (WD), annualized factor costs (AFC) were obtained from the chart records of pre-switch 12 months and post-switch at least more-than 6-month until July, 2019. Data from scheduled operation or hospitalization due to trauma or accidence were excluded. Results: There were 8 boys and 43 adults, the median age of all PwHA when switching was 35.6 years (10.5-62). Before switching, these 51 PTP treated with SHL rFVIII who received ET (ET group), irregular prophylaxis (IP group), and regular prophylaxis (RP group) were 19 (37.3%), 7 (13.7%), and 25 (49%), respectively. Bleeding records of 51 PTP treated with SHL rFVIII were traced back with 11.8±0.9 months. After switching to rFVIII-Fc, 3 PwHA receiving ET were excluded, and bleeding records of 48 received RP were obtained with 14.7±4.6 months. Pre-switch and post-switch prophylaxis rate were 62.7% (32/51) and 94.1% (48/51), respectively. For comparison of pre-switch and post-switch outcomes: Median ABR was reduced from 48, 12, and 4 to 1.15, 1.9, and 1.5 for ET, IP, and RP group, respectively. Median AJBR was reduced from 32, 11, and 4 to 0.95, 0.7, and 1.2 for ET, IP, and RP group, respectively. Median WD was increased from 38.4, 52.9, and 63.6 IU/kg/wk to 84.6, 84.5, and 84.9 IU/kg/wk for ET, IP, and RP group, respectively. Median AFC was increased from 4,141,800, 4,064,000 and 5,129,700 NTD to 7,042,325, 5,835,450, and 5,762,810 NTD for ET, IP, and RP group, respectively. Comparing pre-switch and post-switch outcomes of children and adults who received pre-switch and post-switch prophylaxis, median ABR was reduced from 3 and 5 to 1.35 and 1.85 for children and adults, respectively. Median AJBR was reduced from 3 and 4 to 1.35 and 1.15 for children and adults, respectively. Median WD was increased from 58.8 and 58.3 IU/kg/wk to 87.85 and 83.85 IU/kg/wk for children and adults, respectively. Median AFC was increased from 4,104,225 and 5,879,025 NTD to 4,419,800 and 6,024,916 NTD for children and adults, respectively. For all PwHA, zero ABR accounted for 5.9% (3/51) with pre-switch SHL rFVIII treatment and for 20.8% (10/48) with post-switch rFVIII-Fc prophylaxis. Zero AJBR accounted for 9.8% (5/51) with SHL rFVIII treatment and for 33.3% (16/48) with rFVIII-Fc prophylaxis. For PwHA with pre- and post-switch prophylaxis, zero ABR accounted for 12.5% (1/8) and 8.3% (2/24), respectively, for children and adults on SHL rFVIII prophylaxis and 25% (2/8) and 25% (6/24) respectively, for children and adults on rFVIII-Fc prophylaxis. Zero AJBR accounted for 12.5% (1/8) and 16.7% (4/24), respectively, for children and adults on SHL rFVIII prophylaxis and 25% (2/8) and 37.5% (9/24) respectively, for children and adults on rFVIII-Fc prophylaxis. Conclusion: In real-world setting, for pre-switch ET group, switch to rFVIII-Fc prophylaxis made both mean ABR and AJBR reduced >95%, and mean WD increased >50%. For pre-switch IP group, switch to rFVIII-Fc prophylaxis made both mean ABR and AJBR reduced >80%, and mean WD increased >35%. For pre-switch RP group, switch to rFVIII-Fc prophylaxis made both mean ABR and AJBR also reduced >45%, and mean WD increased >20%. The proportions in zero ABR and zero AJBR as post-switch rFVIII-Fc prophylaxis were increased. No matter in ET, IP, or RP group, after switching to RP with rFVIII-Fc, improvement for bleeding outcomes was quite evident. Disclosures No relevant conflicts of interest to declare.

Baseline VWF:Ag Level and Body Mass Index Are Inverse Influencing Factors of Annualized Total Bleeding Rate and Annualized Joint Bleeding Rate Respectively in Severe-Type Adult Patients with Hemophilia a (PwHA) with Episodic Treatment with rFVIII

Introduction: Bleeding phenotypes of severe-type patients with hemophilia A (PwHA) vary greatly, which influence factor consumption and medical cost. Factors affecting bleeding patterns of PwHA include various procoagulant and anticoagulant factors, joint condition and physical activity, etc. We aimed to investigate clinical factors influencing by-nature bleeding frequency of severe-type PwHA during episodic treatment. Methods and materials: There were 19 non-inhibitor, severe-type, previously treated PwHA aged >20 years, who had at least one to five major joints arthropathy, retrospectively enrolled from two hemophilia centers for analysis. They had been refusing prophylaxis therapy with FVIII product due to heavy burden of frequent intravenous FVIII injection and had long-term episodic treatment. Clinical informations were collected from November 2017 to November 2018, including age, body mass index (BMI), body weight, ABO blood grouping, HCV and HIV infection status, baseline VWF:Ag and VWF:activity, mutation of F8 gene. Annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR), weekly doses and annualized factor consumption costs (calculated by new Taiwan dollars, NTD) were obtained from the patients' medical records. Results: The PwHA with ABR <24 had significantly lower proportion of blood-group-O patients, higher baseline VWF:Ag and VWF:activity than those with ABR >24.(P-value <0.05) The PwHA with AJBR <13 had significantly higher BMI than those with AJBR >13.(P-value <0.05) There was no significant difference in ABR, AJBR, weekly dose, and annualized factor cost between PwHA with O blood group and non-O blood group. Compared with PwHA with baseline VWF:Ag or VWF:activity <145%, those with baseline VWF:Ag or VWF:activity >145% had significantly older age (34.9 vs 53.2 years, P-value <0.05), higher BMI (25.2 vs 29.9, P-value <0.05), lower ABR (58.2 vs 12.2 per year, P-value<0.01), lower AJBR (46.8 vs 10.8 per year, P-value<0.01), lower weekly dose (42.4 vs 10.6 IU/kg/wk, P-value<0.01), and lower annualized factor consumption costs (4,177,732 vs 1,120,704 NTD, P-value<0.01). Compared with PwHA with BMI <28, those with BMI >28 had significantly lower ABR (58.2 vs 12.2 per year, P-value<0.05), lower AJBR (46.8 vs 10.8 per year, P-value<0.05), higher baseline VWF:activity (94.6% vs 190.2%, P-value <0.05), and lower weekly dose (38.5 vs 17.1 IU/kg/wk, P-value <0.05). By backward-stepwise multivariate linear regression, baseline VWF:Ag and BMI were identified as independent and significant inverse influencing factors for ABR and AJBR, respectively.(P-value <0.05) Conclusion: For severe-type adult PwHA with episodic treatment, baseline VWF:Ag or VWF:activity >145% was associated with lower ABR, AJBR, weekly dose, and annualized factor cost. BMI >28 was associated with lower ABR, AJBR, and weekly dose consumption. Baseline VWF:Ag and BMI were revealed as inverse influencing factors for ABR and AJBR, respectively. The results of our study could be useful for clinicians to have an insight into diversity of bleeding phenotypes of by-nature severe-type PwHA. For developing countries where factor concentrate resources are not enough, these clinical influencing factors might be helpful for the management of therapeutic strategies and resource allocation for severe PwHA. Disclosures No relevant conflicts of interest to declare.