Risk factors for renal involvement in Henoch-Schönlein purpura

Abstract Objective: Henoch-Schönlein purpura is a systemic vasculitis that mainly occurs in children. Renal impairment is a major complication of Henoch-Schönlein purpura, but there is no established predictive marker for renal involvement. Thus, in this study, we investigated the risk factors for renal involvement in children with Henoch-Schönlein purpura. Method: The medical records of children newly diagnosed as having Henoch-Schönlein purpura between 2005 and 2020 were reviewed retrospectively. Selected laboratory data were recorded before treatment initiation. The date and the age at diagnosis; sex; and the presence of arthralgia, gastrointestinal and renal involvement were obtained retrospectively. Results: This study included a total of 186 patients with Henoch-Schönlein purpura. Among them, 36.0% had renal involvement; 28.4% had only microscopic hematuria, 53.7% had nonnephrotic range proteinuria, and 17.9% had nephrotic-range proteinuria during follow-up. The mean age was higher (p = 0.016) and female sex was predominant (p = 0.001) in patients with renal involvement than in those without renal involvement. Blood neutrophil/lymphocyte ratio (p = 0.002) and platelet/lymphocyte ratio (p = 0.002) were significantly higher than that of the patients without renal involvement. No statistically significant differences were observed in the hemoglobin concentration, platelet count, presence of arthralgia, and gastrointestinal involvement between patients with and without renal involvement. Logistic regression analysis revealed female sex (odd ratio = 3.213) and neutrophil/lymphocyte ratio (odd ratio = 1.329) as risk factors for renal involvement. Conclusions: Female sex and high neutrophil/lymphocyte ratio were risk factors for renal involvement in Henoch-Schönlein purpura.

Health Care Provider Perceptions of Facilitators and Barriers to Human Papillomavirus Vaccination Delivery in Five Countries.

BACKGROUND: National human papillomavirus (HPV) vaccination programs could reduce global cervical cancer morbidity and mortality with support from health care providers. We assessed providers' perceptions of HPV vaccination in 5 countries. METHODS: We identified providers from 5 countries where national HPV vaccination programs were at various stages of implementation: Argentina, Malaysia, South Africa, South Korea, and Spain. Providers authorized to administer adolescent vaccines completed an in-depth survey, reporting perceptions of barriers and facilitators to initiating and completing HPV vaccination, and logistical challenges to HPV vaccination. RESULTS: Among 151 providers, common barriers to HPV vaccination initiation across all countries were parents' lack of awareness (39%), concerns about vaccine safety or efficacy (33%), and cost to patients (30%). Vaccination education campaign (70%) was the most commonly cited facilitator of HPV vaccination initiation. Common barriers to series completion included no reminder system or dosing schedule (37%), loss to follow-up or forgetting appointment (29%), and cost to patients (25%). Cited facilitators to completing the vaccine series were education campaigns (45%), affordable vaccination (32%), and reminder/recall systems (22%). Among all countries, high cost of vaccination was the most common logistical challenge to offering vaccination to adolescents (33%). CONCLUSIONS: Incorporating provider insights into future HPV vaccination programs could accelerate vaccine delivery to increase HPV vaccination rates globally.

Risk factors for renal involvement in Henoch-Schönlein purpura.

OBJECTIVE: Henoch-Schönlein purpura is a systemic vasculitis that mainly occurs in children. Renal impairment is a major complication of Henoch-Schönlein purpura, but there is no established predictive marker for renal involvement. Thus, in this study, we investigated the risk factors for renal involvement in children with Henoch-Schönlein purpura. METHOD: The medical records of children newly diagnosed as having Henoch-Schönlein purpura between 2005 and 2020 were reviewed retrospectively. Selected laboratory data were recorded before treatment initiation. The date and the age at diagnosis; sex; and the presence of arthralgia, gastrointestinal and renal involvement were obtained retrospectively. RESULTS: This study included a total of 186 patients with Henoch-Schönlein purpura. Among them, 36.0% had renal involvement; 28.4% had only microscopic hematuria, 53.7% had non-nephrotic range proteinuria, and 17.9% had nephrotic-range proteinuria during follow-up. The mean age was higher (p = 0.016) and female sex was predominant (p = 0.001) in patients with renal involvement than in those without renal involvement. Blood neutrophil/lymphocyte ratio (p = 0.002) and platelet/lymphocyte ratio (p = 0.002) were significantly higher than that of the patients without renal involvement. No statistically significant differences were observed in the hemoglobin concentration, platelet count, presence of arthralgia, and gastrointestinal involvement between patients with and without renal involvement. Logistic regression analysis revealed female sex (odd ratio = 3.213) and neutrophil/lymphocyte ratio (odd ratio = 1.329) as risk factors for renal involvement. CONCLUSIONS: Female sex and high neutrophil/lymphocyte ratio were risk factors for renal involvement in Henoch-Schönlein purpura.

Persuasive messaging for human papillomavirus vaccination by adolescent providers in a five-country multi-site study.

OBJECTIVE: Strong persuasive messaging by providers is a key predictor for patient acceptance of prophylactic human papillomavirus vaccination. We aimed to determine optimal messaging to promote human papillomavirus adolescent vaccination across different geographical sites. METHODS: Adolescent providers (n = 151) from Argentina, Malaysia, South Africa, South Korea, and Spain were surveyed on messages, family decision makers, and sources of communication to best motivate parents to vaccinate their adolescent daughters overall, and against human papillomavirus. Multivariate logistic regression assessed the likelihood of recommending messages specifically targeted at cervical cancer with providers' characteristics: gender, medical specialization, and previous administration of human papillomavirus vaccination. RESULTS: Mothers were considered the most important human papillomavirus vaccination decision makers for their daughters (range 93%-100%). Television was cited as the best source of information on human papillomavirus vaccination in surveyed countries (range 56.5%-87.1%), except Spain where one-on-one discussions were most common (73.3%). Prevention messages were considered the most likely to motivate parents to vaccinate their daughters overall, and against human papillomavirus, in all five countries (range 30.8%-55.9%). Optimal messages emphasized cervical cancer prevention, and included strong provider recommendation to vaccinate, vaccine safety and efficacy, timely vaccination, and national policy for human papillomavirus vaccination. Pediatricians and obstetricians/gynecologists were more likely to cite that the best prevention messages should focus on cervical cancer (OR: 4.2, 95% CI: 1.17 to 15.02 vs other medical specialists). CONCLUSIONS: Provider communication messages that would motivate parents to vaccinate against human papillomavirus were based on strong recommendation emphasizing prevention of cervical cancer. To frame convincing messages to increase vaccination uptake, adolescent providers should receive updated training on human papillomavirus and associated cancers, while clearly addressing human papillomavirus vaccination safety and efficacy.

Adolescent providers' knowledge of human papillomavirus vaccination age guidelines in five countries.

Purpose: To examine provider knowledge of HPV vaccination age guidelines in five countries. Methods: A total of 151 providers of adolescent vaccinations in Argentina, Malaysia, South Africa, South Korea, and Spain were interviewed between October 2013 and April 2014. Univariate analyses compared providers' understanding of recommended age groups for HPV vaccination to that of each country's national guidelines. Results: In three of five countries surveyed, most providers (97% South Africa, 95% Argentina, 87% Malaysia) included all nationally recommended ages in their target age group. However, a relatively large proportion of vaccinators in some countries (83% Malaysia, 55% Argentina) believed that HPV vaccination was recommended for women above age 26, far exceeding national guidelines, and beyond the maximum recommended age in the United States. National median minimum and maximum age recommendations cited by the respondents for HPV vaccination were 11 and 29 years in Argentina (national guideline: 11-14), 13 and 48 years in Malaysia (guideline 13-14), 8 and 14 years in South Africa (guideline 9-14), 10 and 20 years in South Korea (guideline 11-14), and 11 and 12 years in Spain (guideline 11-14). In all countries, a higher percentage of vaccinators included all nationally recommended ages for vaccination, as compared to providers who did not administer HPV vaccination. Conclusions: Overall, a substantial proportion of providers incorrectly reported their country's age guidelines for HPV vaccination, particularly the upper age limit. As provider recommendation is among the strongest predictors of successful vaccination uptake among adolescents, improved education and clarification of national guidelines for providers administering HPV vaccination is essential to optimize prevention of infection and associated disease.

Acceptability of two- versus three-dose human papillomavirus vaccination schedule among providers and mothers of adolescent girls: a mixed-methods study in five countries.

PURPOSE: The World Health Organization revised its human papillomavirus (HPV) vaccination recommendations to include a two (2-) dose schedule for girls aged ≤ 15 years. We investigated acceptability of 2- versus 3-dose schedule among adolescent vaccination providers and mothers of adolescent girls in five countries. METHODS: Adolescent vaccination providers (N = 151) and mothers of adolescent girls aged 9-14 years (N = 118) were recruited from Argentina, Malaysia, South Africa, South Korea, and Spain. We assessed providers' preference for a 2- versus 3-dose HPV vaccination schedule via quantitative surveys. Mothers' attitudes towards a 2-dose schedule were assessed through focus group discussions. RESULTS: Most adolescent providers preferred a 2- over a 3-dose HPV vaccination schedule (overall: 74%), with preference ranging from 45.2% (South Africa) to 90.0% (South Korea). Lower cost, fewer clinic visits, and higher series completion were commonly cited reasons for 2-dose preference among providers and mothers. Safety and efficacy concerns were commonly cited barriers to accepting a 2-dose HPV vaccination schedule among providers and mothers. Mothers generally accepted the reduced schedule, however requested further information from a trusted source. CONCLUSIONS: Adolescent vaccination providers and mothers preferred the 2-dose over 3-dose HPV vaccination schedule. Acceptability of a 2-dose HPV vaccination could be improved with additional information to providers and mothers on HPV vaccination safety and efficacy.

HPV Vaccination Recommendation Practices among Adolescent Health Care Providers in 5 Countries.

STUDY OBJECTIVE: To assess adolescent health care providers' recommendations for, and attitudes towards human papillomavirus (HPV) vaccination in 5 countries. DESIGN: In-depth interviews of adolescent health care providers, 2013-2014. SETTING: Five countries where HPV vaccination is at various stages of implementation into national programs: Argentina, Malaysia, South Africa, South Korea, and Spain. PARTICIPANTS: Adolescent health care providers (N = 151) who had administered or overseen provision of adolescent vaccinations (N = Argentina: 30, Malaysia: 30, South Africa: 31, South Korea: 30, Spain: 30). MAIN OUTCOME MEASURES: Frequency of HPV vaccination recommendation, reasons providers do not always recommend the vaccine and facilitators to doing so, comfort level with recommending the vaccine, reasons for any discomfort, and positive and negative aspects of HPV vaccination. RESULTS: Over half of providers 82/151 (54%) recommend HPV vaccination always or most of the time (range: 20% in Malaysia to 90% in Argentina). Most providers 112/151 (74%) said they were comfortable recommending HPV vaccination, although South Korea was an outlier 10/30 (33%). Providers cited protection against cervical cancer 124/151 (83%) and genital warts 56/151 (37%) as benefits of HPV vaccination. When asked about the problems with HPV vaccination, providers mentioned high cost 75/151 (50% overall; range: 26% in South Africa to 77% in South Korea) and vaccination safety 28/151 (19%; range: 7% in South Africa to 33% in Spain). Free, low-cost, or publicly available vaccination 59/151 (39%), and additional data on vaccination safety 52/151 (34%) and efficacy 43/151 (28%) were the most commonly cited facilitators of health provider vaccination recommendation. CONCLUSION: Interventions to increase HPV vaccination should consider a country's specific provider concerns, such as reducing cost and providing information on vaccination safety and efficacy.

Urinary tract infection caused by community-acquired extended-spectrum ß-lactamase-producing bacteria in infants / Infecção do trato urinário causada por bactérias produtoras de ß-lactamase- de espectro ampliado adquiridas na comunidade em neonatos

Abstract Objective: Urinary tract infection (UTI) caused by resistant strains of bacteria is increasingly prevalent in children. The aim of this study was to investigate the clinical characteristics and risk factors for UTI caused by community-acquired extended-spectrum β-lactamase (CA-ESBL)-producing bacteria in infants. Methods: This was a retrospective study performed over 5 years in a single Korean center. Hospitalized infants with febrile UTI were enrolled and divided into two groups (CA-ESBL vs. CA non-ESBL UTI). The yearly prevalence was calculated. Baseline characteristics and clinical course such as fever duration, laboratory and radiological findings were compared between the two groups. Risk factors associated with the CA-ESBL UTI were investigated. Results: Among the enrolled infants (n = 185), 31 (17%) had CA-ESBL UTI. The yearly prevalence of ESBL of CA-ESBL UTI increased during the study (0% in 2010, 22.2% in 2015). Infants with CA-ESBL UTI had a longer duration of fever after initiating antibiotics (2.0 ± 1.1 vs. 1.5 ± 0.6 days, p = 0.020). Cortical defects on renal scan and early treatment failure were more frequent in CA-ESBL (64.5 vs. 42.2%, p = 0.023; 22.6 vs. 4.5%, p = 0.001). A logistic regression analysis revealed that urinary tract abnormalities and previous UTI were independent risk factors for CA-EBSL UTI (odds ratio, 2.7; p = 0.025; 10.3; p = 0.022). Conclusion: The incidence of UTI caused by ESBL-producing bacteria has increased in Korean infants. Recognition of the clinical course and risk factors for ESLB-producing UTI may help to determine appropriate guidelines for its management.

Resumo Objetivo: A infecção do trato urinário (ITU) causada por cepas de bactérias resistentes está cada vez mais prevalente em crianças. O objetivo deste estudo foi investigar as características clínicas e os fatores de risco de ITU causada por bactérias produtoras de β-lactamases de espectro ampliado adquiridas na comunidade (ESBL CA) em neonatos. Métodos: Estudo retrospectivo feito por mais de cinco anos em um único centro sul-coreano. Neonatos internados com ITU febril foram inscritos e divididos em dois grupos (ITU por ESBL CA em comparação com não ESBL CA). A prevalência anual foi calculada. As características básicas e o curso clínico, como duração da febre e achados laboratoriais e radiológicos, foram comparados entre os dois grupos. Os fatores de risco associados à ITU por ESBL CA foram investigados. Resultados: Entre os neonatos inscritos (n = 185), 31 (17%) apresentaram ITU por ESBL CA. A prevalência anual de ESBL em ITU por ESBL CA aumentou durante o estudo (0% em 2010, 22,2% em 2015). Os neonatos com ITU por ESBL CA apresentaram maior duração de febre após o início dos antibióticos (2 ± 1,1 em comparação com 1,5 ± 0,6 dias, p = 0,020). Os defeitos corticais no exame renal e a falha precoce no tratamento foram mais frequentes em ESBL CA (64,5 em comparação com 42,2%, p = 0,023; 22,6 em comparação com 4,5%, p = 0,001). Uma análise de regressão logística revelou que as anomalias do trato urinário e a ITU anterior eram fatores de risco independentes de ITU por ESBL CA (razão de chance: 2,7; p = 0,025; 10,3; p = 0,022). Conclusão: A incidência de ITU causada por bactérias produtoras de ESBL aumentou em neonatos sul-coreanos. O reconhecimento do curso clínico e dos fatores de risco de ITU por ESBL poderá ajudar a determinar as diretrizes adequadas de manejo.

Urinary tract infection caused by community-acquired extended-spectrum ß-lactamase-producing bacteria in infants.

OBJECTIVE: Urinary tract infection (UTI) caused by resistant strains of bacteria is increasingly prevalent in children. The aim of this study was to investigate the clinical characteristics and risk factors for UTI caused by community-acquired extended-spectrum ß-lactamase (CA-ESBL)-producing bacteria in infants. METHODS: This was a retrospective study performed over 5 years in a single Korean center. Hospitalized infants with febrile UTI were enrolled and divided into two groups (CA-ESBL vs. CA non-ESBL UTI). The yearly prevalence was calculated. Baseline characteristics and clinical course such as fever duration, laboratory and radiological findings were compared between the two groups. Risk factors associated with the CA-ESBL UTI were investigated. RESULTS: Among the enrolled infants (n=185), 31 (17%) had CA-ESBL UTI. The yearly prevalence of ESBL of CA-ESBL UTI increased during the study (0% in 2010, 22.2% in 2015). Infants with CA-ESBL UTI had a longer duration of fever after initiating antibiotics (2.0±1.1 vs. 1.5±0.6 days, p=0.020). Cortical defects on renal scan and early treatment failure were more frequent in CA-ESBL (64.5 vs. 42.2%, p=0.023; 22.6 vs. 4.5%, p=0.001). A logistic regression analysis revealed that urinary tract abnormalities and previous UTI were independent risk factors for CA-EBSL UTI (odds ratio, 2.7; p=0.025; 10.3; p=0.022). CONCLUSION: The incidence of UTI caused by ESBL-producing bacteria has increased in Korean infants. Recognition of the clinical course and risk factors for ESLB-producing UTI may help to determine appropriate guidelines for its management.

Low concentrations of doxycycline attenuates FasL-induced apoptosis in HeLa cells.

BACKGROUND: Doxycycline (DC) has been shown to possess non-antibiotic properties including Fas/Fas Ligand (FasL)-mediated apoptosis against several tumor types in the concentration range of 10-40 µg/mL. However, the effect of DC in apoptotic signaling at much low concentrations was not studied. METHODS: The present study investigated the attenuation effect of low dose of DC on FasL-induced apoptosis in HeLa cell by the methods of MTT assay, fluorescence microscopy, DNA fragmentation, flow cytometry analysis, and western blotting. RESULTS AND CONCLUSION: In the present findings we showed that low concentration of DC (<2.0 µg/mL) exhibited protective effects against FasL-induced apoptosis in HeLa cells. FasL treatment to HeLa cells resulted in a concentration-dependent induction of cell death, and treatment with low concentrations of DC (0.1-2 µg/mL) significantly (p < 0.001) attenuated the FasL-induced cell death as measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Further, the FasL-induced apoptotic features in HeLa cells, such as morphological changes, DNA fragmentation and cell cycle arrest was also inhibited by DC (0.5 µg/mL). Tetracycline and minocycline also showed similar anti-apoptotic effects but were not significant when compared to DC, tested at same concentrations. Further, DC (0.01-16 µg/mL) did not influence the hydrogen peroxide- or cisplatin-induced intrinsic apoptotic pathway in HeLa cells. Protein analysis using Western blotting confirmed that FasL-induced cleavage/activation of caspase-8 and caspase-3, were inhibited by DC treatment at low concentration (0.5 µg/mL). Considering the overall data, we report for the first time that DC exhibited anti-apoptotic effects at low concentrations in HeLa cells by inhibition of caspase activation via FasL-induced extrinsic pathway.

Low concentrations of doxycycline attenuates FasL-induced apoptosis in HeLa cells

BACKGROUND: Doxycycline (DC) has been shown to possess non-antibiotic properties including Fas/Fas Ligand (FasL)-mediated apoptosis against several tumor types in the concentration range of 10-40 µg/mL. However, the effect of DC in apoptotic signaling at much low concentrations was not studied. METHODS: The present study investigated the attenuation effect of low dose of DC on FasL-induced apoptosis in HeLa cell by the methods of MTT assay, fluorescence microscopy, DNA fragmentation, flow cytometry analysis, and western blotting. RESULTS AND CONCLUSION: In the present findings we showed that low concentration of DC (<2.0 µg/mL) exhibited protective effects against FasL-induced apoptosis in HeLa cells. FasL treatment to HeLa cells resulted in a concentration-dependent induction of cell death, and treatment with low concentrations of DC (0.1-2 µg/mL) significantly (p < 0.001) attenuated the FasL-induced cell death as measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazo-lium bromide (MTT) assay. Further, the FasL-induced apoptotic features in HeLa cells, such as morphological changes, DNA fragmentation and cell cycle arrest was also inhibited by DC (0.5 µg/mL). Tetracycline and minocycline also showed similar anti-apoptotic effects but were not significant when compared to DC, tested at same concentrations. Further, DC (0.01-16 µg/mL) did not influence the hydrogen peroxide- or cisplatin-induced intrinsic apoptotic pathway in HeLa cells. Protein analysis using Western blotting confirmed that FasL-induced cleavage/activation of cas-pase-8 and caspase-3, were inhibited by DC treatment at low concentration (0.5 µg/mL). Considering the overall data, we report for the first time that DC exhibited anti-apoptotic effects at low concentrations in HeLa cells by inhibition of caspase activation via FasL-induced extrinsic pathway.

Nonclassic congenital lipoid adrenal hyperplasia: a new disorder of the steroidogenic acute regulatory protein with very late presentation and normal male genitalia.

CONTEXT: Lipoid congenital adrenal hyperplasia is a severe disorder of adrenal and gonadal steroidogenesis caused by mutations in the steroidogenic acute regulatory protein (StAR). Affected children typically present with life-threatening adrenal insufficiency in early infancy due to a failure of glucocorticoid (cortisol) and mineralocorticoid (aldosterone) biosynthesis, and 46,XY genetic males have complete lack of androgenization and appear phenotypically female due to impaired testicular androgen secretion in utero. OBJECTIVE: The objective of this study was to investigate whether nonclassic forms of this condition exist. PATIENTS AND METHODS: Sequence analysis of the gene encoding StAR was undertaken in three children from two families who presented with primary adrenal insufficiency at 2-4 yr of age; the males had normal genital development. Identified mutants were tested in a series of biochemical assays. RESULTS: DNA sequencing identified homozygous StAR mutations Val187Met and Arg188Cys in these two families. Functional studies of StAR activity in cells and in vitro and cholesterol-binding assays showed these mutants retained approximately 20% of wild-type activity. CONCLUSIONS: These patients define a new disorder, nonclassic lipoid congenital adrenal hyperplasia, and represent a new cause of nonautoimmune Addison disease (primary adrenal failure).