Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant morbidity and mortality worldwide. Despite a successful vaccination programme, the emergence of mutated variants that can escape current levels of immunity mean infections continue. Herein, we report the development of CT-P63, a broad-spectrum neutralizing monoclonal antibody. In vitro studies demonstrated potent neutralizing activity against the most prevalent variants, including Delta and the BA.1 and BA.2 sub-lineages of Omicron. In a transgenic mouse model, prophylactic CT-P63 significantly reduced wild-type viral titres in the respiratory tract and CT-P63 treatment proved efficacious against infection with Beta, Delta, and Omicron variants of SARS-CoV-2 with no detectable infectious virus in the lungs of treated animals. A randomized, double-blind, parallel-group, placebo-controlled, Phase I, single ascending dose study in healthy volunteers (NCT05017168) confirmed the safety, tolerability, and pharmacokinetics of CT-P63. Twenty-four participants were randomized and received the planned dose of CT-P63 or placebo. The safety and tolerability of CT-P63 were evaluated as primary objectives. Eight participants (33.3%) experienced a treatment-emergent adverse event (TEAE), including one grade ≥3 (blood creatine phosphokinase increased). There were no deaths, treatment-emergent serious adverse events, TEAEs of special interest, or TEAEs leading to study drug discontinuation in the CT-P63 groups. Serum CT-P63 concentrations rapidly peaked before declining in a biphasic manner and systemic exposure was dose proportional. Overall, CT-P63 was clinically safe and showed broad-spectrum neutralizing activity against SARS-CoV-2 variants in vitro and in vivo.

Effects on inequality in life expectancy from a social ecology perspective.

BACKGROUND: Inequality in life expectancy (ILE) is defined as inequality in the distribution of expected span of life-based on data from survival tables estimated using the Atkinson inequality index. ILE can be influenced by socio-ecological indicators including the Gini coefficient, secondary education, output per worker, and old age pension. This study examined the effects on ILE from a social ecology perspective. METHODS: This analysis is based on ILE data from 108 countries obtained from the United Nations Development Programme. Data on socio-ecological indicators were obtained from the United Nations database. The associations between socio-ecological indicators and ILE were assessed using correlation coefficients and multiple regression models. RESULTS: Significant correlations were evident between ILE and the following indicators from a socio-ecological perspective: Gini coefficient (GC: r = 0.335, p = 0.001) as an indicator of income inequality, female population with at least some secondary education (FSE: r = - 0.757, p = 0.001), male population with at least some secondary education (MSE: r = - 0.741, p = 0.001), output per worker as a measure of labor productivity (OPW: r = - 0.714, p = 0.001), and number of old age pension recipients (OPR: r = - 0.641, p = 0.001). In multivariate regression, the ILE predictors were higher GC and lower levels of FSE, MSE, OPW, and OPR (R2 = 0.648, p < 0.001). CONCLUSIONS: Socio-ecological factors have an important effect on ILE. Policies that address ILE should consider targeted socio-ecological factors, such as the Gini coefficient of income inequality, that give a personal perspective of economic deprivation, attainment of at least a secondary education by both females and males that gives a social environment perspective, output per worker that indicates labor productivity, and the number of old age pension recipients that indicates social security from a public policy perspective.

Socio-ecological perspective of older age life expectancy: income, gender inequality, and financial crisis in Europe.

BACKGROUND: Population is aging rapidly in Europe. Older age life expectancy (OLE) can be influenced by country-level depth of credit information (DCI) as an indicator of financial crisis, gross national income (GNI) per capita, and gender inequality index (GII). These factors are key indicators of socio-ecological inequality. They can be used to develop strategies to reduce country-level health disparity. The objective of this study was to confirm the relationship between socio-ecological factors and OLE in Europe. METHODS: Data were obtained from World Bank, WHO, and UN database for 34 Europe countries. Associations between socio-ecological factors and OLE were assessed with Pearson correlation coefficients and three regression models. These models assumed that appropriate changes in country-level strategies of healthy aging would produce changes in GNI per capital as personal perspective, GII in social environment perspective, and DCI in public policy perspective to implement socio-ecological changes. Hierarchal linear regression was used for final analysis. RESULTS: Although OLE (women and men) had significant negative correlation with GII (gender inequality index, r = - 0.798, p = 0.001), it had positive correlations with GNI (gross national income per capita, r = 0.834, p = 0.001) and DCI (depth of credit information index, r = 0.704, p = 0.001) levels caused by financial crisis. Higher levels GNI and DCI but lower GII were found to be predictors of OLE (women and men) (R2 = 0.804, p < 0.001). CONCLUSIONS: Factors affecting older age life expectancy in Europe were identified from socio-ecological perspective. Socio-ecological indicators (GII, GNI, and DCI) in Europe appear to have a latent effect on OLE levels. Thus, country-level strategies of successful aging in Europe should target socio-ecological factors such as GII, GNI, and DCI value.

COUNTRY-LEVEL SOCIOECONOMIC INDICATORS ASSOCIATED WITH SURVIVAL PROBABILITY OF BECOMING A CENTENARIAN AMONG OLDER EUROPEAN ADULTS: GENDER INEQUALITY, MALE LABOUR FORCE PARTICIPATION AND PROPORTIONS OF WOMEN IN PARLIAMENTS.

This study confirms an association between survival probability of becoming a centenarian (SPBC) for those aged 65 to 69 and country-level socioeconomic indicators in Europe: the gender inequality index (GII), male labour force participation (MLP) rates and proportions of seats held by women in national parliaments (PWP). The analysis was based on SPBC data from 34 countries obtained from the United Nations (UN). Country-level socioeconomic indicator data were obtained from the UN and World Bank databases. The associations between socioeconomic indicators and SPBC were assessed using correlation coefficients and multivariate regression models. The findings show significant correlations between the SPBC for women and men aged 65 to 69 and country-level socioeconomic indicators: GII (r=-0.674, p=0.001), MLP (r=0.514, p=0.002) and PWP (r=0.498, p=0.003). The SPBC predictors for women and men were lower GIIs and higher MLP and PWP (R 2=0.508, p=0.001). Country-level socioeconomic indicators appear to have an important effect on the probability of becoming a centenarian in European adults aged 65 to 69. Country-level gender equality policies in European counties may decrease the risk of unhealthy old age and increase longevity in elders through greater national gender equality; disparities in GII and other country-level socioeconomic indicators impact longevity probability. National longevity strategies should target country-level gender inequality.

Relationship Between the Remaining Years of Healthy Life Expectancy in Older Age and National Income Level, Educational Attainment, and Improved Water Quality.

The remaining years of healthy life expectancy (RYH) at age 65 years can be calculated as RYH (65) = healthy life expectancy-aged 65 years. This study confirms the associations between socioeconomic indicators and the RYH (65) in 148 countries. The RYH data were obtained from the World Health Organization. Significant positive correlations between RYH (65) in men and women and the socioeconomic indicators national income, education level, and improved drinking water were found. Finally, the predictors of RYH (65) in men and women were used to build a model of the RYH using higher socioeconomic indicators (R(2 )= 0.744, p < .001). Overall country-level educational attainment, national income level, and improved water quality influenced the RYH at 65 years. Therefore, policymaking to improve these country-level socioeconomic factors is expected to have latent effects on RYH in older age.

Social Structural Influences on Healthy Aging: Community-Level Socioeconomic Conditions and Survival Probability of Becoming a Centenarian for Those Aged 65 to 69 in South Korea.

This study estimated the associations between community-level socioeconomic conditions and survival probability of becoming a centenarian (SPBC) for those aged 65 to 69 in South Korea to determine the social structural influences on healthy aging. The indicators of socioeconomic and data of centenarians were obtained from Statistics Korea database 2014: population census and social survey. Significant positive correlations were found between SPBC and community-level socioeconomic conditions (minimum cost of living and economically active population, water supply and sewerage, pave a road with asphalt, and urbanization). SPBC male and female predictors had higher economic level and base facilities (R2)=0.578, p<.001). The study provides evidence that community-level socioeconomic conditions are important correlates of SPBC for those aged 65 to 69 in South Korea. These strategies should include social structural influences on successful aging in the overall socioeconomic conditions.

Labor force participation and secondary education of gender inequality index (GII) associated with healthy life expectancy (HLE) at birth.

BACKGROUND: What is the factor that affects healthy life expectancy? Healthy life expectancy (HLE) at birth may be influenced by components of the gender inequality index (GII). Notably, this claim is not tested on the between components of the GII, such as population at least secondary education (PLSE) with ages 25 and older, labor force participation rate (LFPR) with ages 15 and older, and the HLE in the world's countries. Thus, this study estimates the associations between the PLSE, LFPR of components of the GII and the HLE. METHODS: The data for the analysis of HLE in 148 countries were obtained from the World Health Organization. Information regarding the GII indicators for this study was obtained from the United Nations database. Associations between these factors and HLE were assessed using Pearson correlation coefficients and regression models. RESULTS: Although significant negative correlations were found between HLE and the LFPR, positive correlations were found between HLE and PLSE. Finally, the HLE predictors were used to form a model of the components of the GII, with higher PLSE as secondary education and lower LFPR as labor force (R(2) = 0.552, P <0.001). CONCLUSIONS: Gender inequality of the attainment secondary education and labor force participation seems to have an important latent effect on healthy life expectancy at birth. Therefore, in populations with high HLE, the gender inequalities in HLE are smaller because of a combination of a larger secondary education advantage and a smaller labor force disadvantage in male-females.

Factors affecting the survival probability of becoming a centenarian for those aged 70, based on the human mortality database: income, health expenditure, telephone, and sanitation.

BACKGROUND: What are the factors that affect the survival probability of becoming a centenarian for those aged 70? Do the factors include income, health expenditure, the use of mobile telephones, or sanitation? The survival probability of becoming a centenarian (SPBC) is defined as an estimate of the production of centenarians by a population. The SPBC (70) is the survival probability of becoming a centenarian for those aged 70. This study estimates the associations between the SPBC (70), and the gross national income, health expenditure, telecommunications, and sanitation facilities in 32 countries. METHODS: The socioeconomic indicators for this study were obtained from the database of the United Nations Development Programme. In addition, the data for the analysis of centenarians in 32 countries were obtained from the Human Mortality Database, which is maintained by the Department of Demography at the University of California, Berkeley, USA, and the Max Planck Institute for Demographic Research in Rostock, Germany. Associations between socioeconomic indicators and SPBC (70) were assessed using Pearson's correlation coefficients and multiple regression models. RESULTS: Significant positive correlations were found between the SPBC (70), and the socioeconomic factors of gross national income (GNI), public expenditure on health as a percentage of gross domestic product (PEHGDP), fixed and mobile telephone subscribers (FMTS) as the standard of living, and improved sanitation facilities (ISF). Overall, the SPBC (70) of female and male predictors were used, in order to form a model production of centenarians, with higher GNI and PEHGDP, as well as higher FMTS and ISF as the socioeconomic factors (R²= 0.422, P< 0.001). CONCLUSIONS: The socioeconomic level in all 32 countries appears to have an important latent effect on the production of centenarians in both females and males. This study has identified the following four important aspects of socioeconomic indicators in the survival probability of becoming a centenarian for those aged 70: higher overall economic development level, public expenditure on health, mobile telephone subscribers as the standard of living, and the use of improved sanitation facilities for healthy aging. Thus, the socioeconomic level seems to affect an important on the survival probability of becoming a centenarian.

Serial assessment of weight-bearing lower extremity alignment radiographs after open-wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to perform a serial assessment of the radiologic parameters of the mechanical axis (MA) and the weight-bearing line (WBL) using a weight-bearing anteroposterior (AP) long-standing view of the lower extremity to determine whether the postoperative MA and WBL change with time. METHODS: A total of 90 consecutive lower limbs were examined retrospectively from a weight-bearing AP long-standing view of the lower extremity obtained from 120 patients who underwent open-wedge high tibial osteotomy (OWHTO). A total of 30 patients were excluded because of (1) complications (7 patients) such as bone graft collapse or broken screws, malunion, or nonunion arising after surgery and (2) no acquisition of a regular series of weight-bearing AP long-standing views of the lower extremity (23 patients). The AP long-standing view of the lower extremity was taken, and weight-bearing AP long-standing views of the lower extremity at 1 month, 6 months, 1 year, and 2 years postoperatively were used for assessment of serial change. The Picture Archiving Communication System (Marotech, Inc, St-Augustin-de-Desmaures, Quebec, Canada) was used for radiologic measurements of the WBL ratio and MA. Serial changes were compared between 1 month, 6 months, 1 year, and 2 years postoperatively. RESULTS: The WBL ratio progressively shifted medially, with significant changes at all time points until 1 year postoperatively (1 month to 6 months, P = .04; 6 months to 1 year, P = .04; 1 year to 2 years, P = .22). Even though the MA angle showed a similar decreasing trend, it showed no statistical difference (P > .05). CONCLUSIONS: This study showed that after OWHTO, the WBL shifts progressively medially until 1 year postoperatively. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Social factors associated with centenarian rate (CR) in 32 OECD countries.

BACKGROUND: Over the last fifty years, the number of centenarians has dramatically increased. The centenarian rate (CR) is representative of the general longevity prevalent in a nation; it indicates the number of individuals aged 100 years or above at a given date divided by the size of the corresponding cohort of a given age. Two important attributes of the CR (50-54) are that it reflects both unchanged age-specific fertility and the absence of migration in populations. It can generally be used in longevity-based evaluations of the broader concept of successful ageing. As such, this retrospective analysis of the social factors that contribute to the CR (50-54) may help to identify the factors associated with successful ageing.This study estimates the CR (50-54) and elucidates the influence of social factors on successful ageing and the CR (50-54), examining 32 member countries of the Organization for Economic Co-operation and Development (OECD). METHODS: The social indicators for this study were obtained from the United Nations database. The data for the analysis of centenarians in the 32 OECD countries were obtained from the world population prospects conducted by the United Nations. Associations between social factors and CR (50-54) were assessed using Pearson correlation coefficients and regression models. RESULTS: Significant positive correlations were found between the CR (50-54) and the social factors of expenditure on health as a percentage of gross domestic product (HEGDP: r = 0.411, p < 0.021), general government expenditure on health as a percentage of total government expenditure (GGEH: r = 0.474, p < 0.006), the proportion of fixed-telephone subscriptions in the population (FTS: r = 0.489, p < 0.005), and the human development index (HDI: r = 0.486, p < 0.005). Finally, these CR (50-54) predictors were used to form a model of successful ageing, with higher HEGDP and GGEH as health expenditure, higher FTS as standard of living, and higher HDI as social well-being (R2 = 0.573, P < 0.025). CONCLUSIONS: The findings suggest that an increased CR (50-54) is affected by multiple social factors involved in successful ageing. Therefore, if they wish to improve their country's CR (50-54), governments must strengthen their existing support services for the elderly through making improvements to standards of living, social well-being and through increased financing of the health sector.

Acupuncture for symptom management in hemodialysis patients: a prospective, observational pilot study.

OBJECTIVES: Patients undergoing hemodialysis suffer from a variety of complications related to end-stage renal disease. This prospective, observational pilot study aims to determine the feasibility, safety, and possible benefits of acupuncture for symptom management in patients undergoing hemodialysis. METHODS: Twenty-four (24) patients undergoing hemodialysis received acupuncture treatment for their symptoms. Manually stimulated, individualized acupuncture treatments were provided twice a week for 6 consecutive weeks on a nondialysis day or on the day of hemodialysis prior to initiating treatment. Symptoms were evaluated using the Measure Your Medical Outcome Profiles 2 questionnaire, and quality of life was measured by Kidney Disease Quality of Life-Short Form (KDQOL-SF(™)) Version 1.3 at baseline, 7 weeks and 11 weeks from baseline. Statistical analysis was conducted on the basis of the intention-to-treat principle. RESULTS: Twenty-one (21) patients (87%) completed the whole treatment course and follow-up evaluation. Three (3) patients dropped out due to increased fatigue (n = 1), pancreatic and renal transplantation (n = 1), and infections of the arteriovenous fistula used for hemodialysis access (n = 1). Patients experienced a significant improvement of symptoms considered the most bothersome, reporting a decrease of 1.87 and 2.08 points on a 0-6 symptom scale at 7 weeks and 11 weeks, respectively (both p < 0.0001). Some subscales of KDQOL-SF(™) showed significant improvement at 7 weeks (effects of kidney disease, burden of kidney disease, role-limitations physical, emotional well-being, and energy/fatigue) and 11 weeks (physical functioning and energy/fatigue). No serious adverse events related to acupuncture occurred. CONCLUSIONS: Acupuncture seems feasible and safe for symptom management in patients undergoing hemodialysis. Future controlled trials are needed to confirm the benefits of acupuncture.

Massage therapy for children with autism spectrum disorders: a systematic review.

OBJECTIVE: We aimed to assess the effectiveness of massage as a treatment option for autism. DATA SOURCES: We searched the following electronic databases using the time of their inception through March 2010: MEDLINE, AMED, CINAHL, EMBASE, PsycINFO, Health Technology Assessment, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Psychology and Behavioral Sciences Collection, 6 Korean medical databases (KSI, DBpia, KISTEP, RISS, KoreaMed, and National Digital Library), China Academic Journal (through China National Knowledge Infrastructure), and 3 Japanese medical databases (Journal@rchive, Science Links Japan, and Japan Science & Technology link). The search phrase used was "(massage OR touch OR acupressure) AND (autistic OR autism OR Asperger's syndrome OR pervasive developmental disorder)." The references in all located articles were also searched. No language restrictions were imposed. STUDY SELECTION: Prospective controlled clinical studies of any type of massage therapy for autistic patients were included. Trials in which massage was part of a complex intervention were also included. Case studies, case series, qualitative studies, uncontrolled trials, studies that failed to provide detailed results, and trials that compared one type of massage with another were excluded. DATA EXTRACTION: All articles were read by 2 independent reviewers (M.S.L. and J-I.K.), who extracted data from the articles according to predefined criteria. Risk of bias was assessed using the Cochrane classification. RESULTS: Of 132 articles, only 6 studies met our inclusion criteria. One randomized clinical trial found that massage plus conventional language therapy was superior to conventional language therapy alone for symptom severity (P < .05) and communication attitude (P < .01). Two randomized clinical trials reported a significant benefit of massage for sensory profile (P < .01), adaptive behavior (P < .05), and language and social abilities (P < .01) as compared with a special education program. The fourth randomized clinical trial showed beneficial effects of massage for social communication (P < .05). Two nonrandomized controlled clinical trials suggested that massage therapy is effective. However, all of the included trials have high risk of bias. The main limitations of the included studies were small sample sizes, predefined primary outcome measures, inadequate control for nonspecific effects, and a lack of power calculations or adequate follow-up. CONCLUSIONS: Limited evidence exists for the effectiveness of massage as a symptomatic treatment of autism. Because the risk of bias was high, firm conclusions cannot be drawn. Future, more rigorous randomized clinical trials seem to be warranted.