Review on epidemiology, disease burden, and treatment patterns of IgA nephropathy in select APAC countries.

BACKGROUND: Immunoglobulin type A (IgA) nephropathy is the most common primary glomerulonephritis (GN) worldwide with higher rates in East and Pacific Asia compared to North America and Europe. Despite high reported prevalence of IgAN in these countries, the overall disease prevalence across Asia is not available. Treatment patterns of IgAN patients across Asian countries have also not been summarized. The aim of this study was to review and summarize evidence on IgA nephropathy prevalence, treatment patterns, and humanistic and economic burden in mainland China, Taiwan, South Korea, Japan, and Australia. METHODS: A targeted literature review was conducted in PubMed and local databases in China (including Taiwan), South Korea, Japan, and Australia between January 2010-December 2021. Website literature searches were conducted using Google Scholar and Baidu. RESULTS: Sixty-nine publications and 3 clinical guidelines were included. Incidence ranged from 0 to 10.7 per 100 000 people per year in Australia, Japan, and Taiwan, and ranged from 6.3 to 24.70% among patients who underwent renal biopsy in mainland China. Prevalence and diagnosis rates ranged from 0 to 72.1% in mainland China, South Korea, Taiwan, Japan, and Australia. Mortality rates in mainland China, South Korea, and Japan varied widely. The top 3 commonly used therapies were angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (0.9-99.6%), corticosteroids (3.5-100%), and immunosuppressants (1.6-85.5%) in Japan, mainland China, and South Korea. Patient quality of life was measured by different tools, and annual hospitalization costs ranged from $1 284.73 to $2 252.12 (2015-2018) in China. CONCLUSIONS: The prevalence of IgA nephropathy among the general population in select countries/regions is not commonly available, despite evidence from studies and clinical guidelines. In addition, it is observed across geographic regions that heterogeneity exists in prevalence rates, and large variations exist in treatment patterns. There is need to fill in these gaps to understand the contributing factors behind the differences through population-based, multi-center, and real-world studies.

A review of health-related quality of life associated with pneumococcal disease: pooled estimates by age and type of disease.

BACKGROUND: Estimates in the research literature on the health-related quality of life (QOL) associated with pneumococcal disease exhibit variation. It complicates the selection of estimates in modeling projects that evaluate the health impact and economic value of the prevention and treatment. This study reviewed the literature and developed pooled QOL estimates associated with pneumococcal disease states. METHODS: We searched peer-reviewed literature for studies that reported pneumococcal disease-related QOL estimates. For each study, we extracted QOL estimates and categorized by age group and disease state. QOL estimates were converted to quality-adjusted life-years (QALYs). Pooled QALY estimates were calculated using simple average, sample-size weighting and inverse-variance weighting. RESULTS: From 18 studies, we organized QOL estimates into 20 groups based on age and disease state. We observed the largest within-disease state variations of QALY estimates in meningitis-related disease states compared to other disease states. Across all age-disease state categories, the pooled QALY estimates ranged from 0.39 for meningitis with long-term sequelae among 0- to 18-year-olds, to 1.00 for non-inpatient pneumonia among 0- to 18-year-olds. CONCLUSIONS: Our results indicated disparities in QOL estimates associated with pneumococcal disease from the literature. Pooled estimates provided a source of consistency that can be used in future modeling efforts.

Real-World Treatment Outcomes Associated With Early Versus Delayed Vedolizumab Initiation in Patients With Ulcerative Colitis.

Background: Patients with ulcerative colitis (UC) typically receive a targeted inflammatory bowel disease therapy after treatment with conventional therapies and after the development of significant morbidity. Evidence suggests that early biologic treatment after diagnosis could improve treatment response and prevent disease complications compared with delayed biologic treatment after conventional therapy. Methods: RALEE was a retrospective study using claims data from IBM® MarketScan® Research Databases between January 1, 2016 and December 31, 2019. Adults with UC and at least one claim for vedolizumab were categorized into Early or Delayed Vedolizumab groups according to whether they had received vedolizumab within 30 days of diagnosis or after conventional therapy (5-aminosalicylates, corticosteroids, and immunomodulators), respectively. Treatment response was assessed at 2, 6, and 12 months after vedolizumab treatment initiation and was analyzed with logistic regression (bivariate). Results: At 2 months, Delayed Vedolizumab was associated with significantly higher odds of nonresponse than Early Vedolizumab (odds ratio [OR], 2.509; 95% confidence interval [CI], 1.28-4.90). Delayed Vedolizumab was not significantly associated with odds of nonresponse at 6 months (OR, 1.173; 95% CI, 0.72-1.90) or at 12 months (OR, 0.872; 95% CI, 0.55-1.37). Mean total healthcare costs were similar in the Early Vedolizumab ($6492) and Delayed Vedolizumab ($5897) groups, although there were small differences in costs from different types of claims. Conclusions: Patients who received vedolizumab early after UC diagnosis were less likely to experience nonresponse at 2 months and incurred similar healthcare costs at 12 months compared with patients who received delayed vedolizumab.

Primary Care Use Among Commercially Insured Adolescents: Evidence From the 2018 Healthcare Effectiveness Data and Information Set.

INTRODUCTION: Improving the utilization of preventive care among adolescents is important for achieving individual-level and population-level health goals. The Healthcare Effectiveness Data and Information Set reports data submitted by managed care health plans, capturing a large number of individuals in the U.S. METHODS: Using Healthcare Effectiveness Data and Information Set from 2018, mean performance levels were calculated for 5 preventive care measures among adolescents. Differences in performance between states that use Healthcare Effectiveness Data and Information Set or Health Plan Accreditation and those that use neither were estimated. Analysis was conducted in January-July 2020. RESULTS: The sample included data from 39 states, with 32 that use Healthcare Effectiveness Data and Information Set or Health Plan Accreditation and 7 that do not. Adolescent vaccination coverage was 28% for the complete human papillomavirus series, 81% for meningococcal, and 88% for tetanus, diphtheria, and acellular pertussis. Access to a primary care practitioner (a 2-year measure) was 91%, and well-care visits (a 1-year measure) were 50%. When compared with states that do not use Healthcare Effectiveness Data and Information Set or Health Plan Accreditation, the mean performance of states that used either Healthcare Effectiveness Data and Information Set or Health Plan Accreditation was statistically significantly higher for 4 of the 5 assessed measures. CONCLUSIONS: Healthcare Effectiveness Data and Information Set measures can help public health officials to monitor progress toward health goals, such as Healthy People 2020, and identify poorly performing health plans and types of preventive services in greatest need of improvement. States using Healthcare Effectiveness Data and Information Set or Health Plan Accreditation were associated with better performance in some adolescent measures, which suggests that health plan accountability may have a role in achieving health outcomes and could be an important area for future research.

Insurance reimbursements for recombinant zoster vaccine in the private sector.

A two-dose series of the recombinant zoster vaccine (RZV, Shingrix) was licensed by the Food and Drug Administration in 2017 and recommended by the Advisory Committee on Immunization Practices in 2018 for adults in the United States age 50 years and older. Despite the health benefits of shingles vaccination, coverage has remained low, with financial barriers among healthcare providers identified as one potential factor. This study estimates the reimbursement levels for RZV among a large sample of privately insured individuals in the US from the 2018 IBM® MarketScan® Commercial Claims and Encounters database. Of 198,534 claims for an RZV dose, the mean reimbursement was $149. Most claims (83%) exceeded $140, which was the private sector vaccine price reported on the CDC vaccine price list in April 2018. These results can be useful for providers considering procuring RZV and for state immunization programs considering ways to improve vaccination coverage.

Costs of Interventions to Increase Vaccination Coverage Among Children in the United States: A Systematic Review.

BACKGROUND: The Community Preventive Services Task Force (CPSTF) has recommended several interventions that have been demonstrated to be effective at increasing vaccination coverage. OBJECTIVE: Conduct a systematic review to examine the costs of interventions designed to increase vaccination coverage among children and adolescents in the United States. DATA SOURCES: PubMed, EconLit, Embase, and Cochrane. STUDY ELIGIBILITY, PARTICIPANTS, AND INTERVENTIONS: Peer-reviewed articles from January 1, 2009 to August 31, 2019. APPRAISAL AND SYNTHESIS METHODS: Studies were identified with systematic searches of the literature, reviewed for inclusion criteria, abstracted for data on intervention, target population, costs, and risk of bias. Cost measures were reported as costs per child in the target population, costs per vaccinated child, incremental costs per vaccinated child, and costs per vaccine dose administered. Results were stratified by intervention type, vaccine, and age group. RESULTS: Thirty-seven studies were identified for full-text review. Across all interventions and age groups, the cost per child ranged from $0.10 to $537.38, and the incremental cost per vaccinated child ranged from $6.52 to $5,098.57. Provider assessment and feedback interventions had the lowest (median) cost per child ($0.17) and a healthcare system-based combined intervention with multiple components had the lowest (median) incremental cost per vaccinated child ($26.65). A community-based combined intervention with multiple components had the highest median cost per child ($537.38) and the highest median incremental cost per vaccinated child ($5,098.57). LIMITATIONS: A small number of included intervention types and inconsistent cost definition. CONCLUSIONS: There is substantial variability in the costs of CPSTF-recommended interventions.

Association between patient psychosocial characteristics and receipt of in-center nocturnal hemodialysis among prevalent dialysis patients.

INTRODUCTION: Compared to traditional in-center hemodialysis (HD), in-center nocturnal dialysis (INHD) is characterized by longer sessions and nighttime administration, which may lead to better outcomes for some patients. Given the importance of patient choice in the decision to initiate INHD, we explored associations between patients' psychosocial characteristics and their receipt of INHD. METHODS: Among hemodialysis patients at a medium-sized dialysis organization, we identified INHD patients as those for whom ≥80% of dialysis sessions were INHD sessions-starting at 6:30 pm or later and lasting ≥5 hours-over the 3 months (≥20 sessions total) after their first INHD session. We extracted dialysis session data from electronic medical records and psychosocial data from social worker assessments. We tested associations of patients' psychosocial characteristics-as well as demographic and clinical characteristics-with INHD receipt among all hemodialysis patients (INHD and HD) in bivariate analyses and multivariable logistic regression models. FINDINGS: Among 759 patients with complete data, we identified 47 (6.2%) as INHD patients. On average, these patients were more likely than HD patients to be employed (full-time 10.6% vs. 5.2%; part-time 17.0% vs. 4.2%; P < 0.001), and they were significantly less likely to require ambulatory assistance (14.9% vs. 39.6%, P < 0.001). In multivariable regressions, we found that part-time employment (versus being unemployed) was associated with a 7.1 percentage-point higher likelihood of being an INHD patient (P = 0.01), and the negative association with ambulatory assistance needs approached statistical significance (P = 0.056). No other psychosocial factors included in this main regression analysis were statistically significantly associated with INHD patient status. DISCUSSION: Researchers comparing the outcomes of patients undergoing INHD versus other treatment modalities will need to account for differences in employment status-and other factors like requiring ambulatory assistance and age which may predict the ability to work-between INHD users and comparison patients to avoid bias in estimates.

Is the High Frequency of Machado-Joseph Disease in China Due to New Mutational Origins?

Machado-Joseph disease (MJD, also known as spinocerebellar ataxia 3 or SCA3) is the most common dominant ataxia worldwide, with an overall average prevalence of 1-5/100,000. To this date, two major ancestral lineages have been found throughout the world. In China, the relative frequency of MJD among the SCAs reaches as high as 63%, however, little is known about its mutational origin in this country. We analyzed 50 families with MJD patients in two or more generations to study the hypothesis that new mutational events have occurred in this population. Haplotypes based on 20 SNPs have shown new genetic backgrounds segregating with MJD mutations in our cohort from China. We found the "Joseph-derived" lineage (Joseph lineage with a G variant in rs56268847) to be very common among Chinese MJD patients. Moreover, we estimated the time for the origin of this MJD SNP background based on STR diversity flanking the (CAG)n of ATXN3. It was surprising to find that the Chinese MJD population originated from 8,000 to 17,000 years ago, far earlier than the previous literature reports, which will be an important evidence to explain the origin, spread and founder effects of MJD.

Identification of a de novo DYNC1H1 mutation via WES according to published guidelines.

De novo mutations that contribute to rare Mendelian diseases, including neurological disorders, have been recently identified. Whole-exome sequencing (WES) has become a powerful tool for the identification of inherited and de novo mutations in Mendelian diseases. Two important guidelines were recently published regarding the investigation of causality of sequence variant in human disease and the interpretation of novel variants identified in human genome sequences. In this study, a family with supposed movement disorders was sequenced via WES (including the proband and her unaffected parents), and a standard investigation and interpretation of the identified variants was performed according to the published guidelines. We identified a novel de novo mutation (c.2327C > T, p.P776L) in DYNC1H1 gene and confirmed that it was the causal variant. The phenotype of the affected twins included delayed motor milestones, pes cavus, lower limb weakness and atrophy, and a waddling gait. Electromyographic (EMG) recordings revealed typical signs of chronic denervation. Our study demonstrates the power of WES to discover the de novo mutations associated with a neurological disease on the whole exome scale, and guidelines to conduct WES studies and interpret of identified variants are a preferable option for the exploration of the pathogenesis of rare neurological disorders.

Primary erythromelalgia: a review.

Primary erythromelalgia (PE ORPHA90026) is a rare autosomal dominant neuropathy characterized by the combination of recurrent burning pain, warmth and redness of the extremities. The incidence rate of PE ranges from 0.36 to 1.1 per 100,000 persons. Gender ratio differs according to different studies and no evidence showed a gender preference. Clinical onset of PE is often in the first decade of life. Burning pain is the most predominant symptom and is usually caused and precipitated by warmth and physical activities. Reported cases of PE contain both inherited and sporadic forms. Genetic etiology of PE is mutations on SCN9A, the encoding gene of a voltage-gated sodium channel subtype Nav1.7. Diagnosis of PE is made upon clinical manifestations and screening for mutations on SCN9A. Exclusion of several other treatable diseases/secondary erythromelalgia is also necessary because of the lack of biomarkers specifically for PE. Differential diagnoses can include Fabry disease, cellulites, Raynaud phenomenon, vasculitis and so on. Diagnostic methods often involve complete blood count, imaging studies and thermograph. Treatment for PE is unsatisfactory and highly individualized. Frequently used pain relieving drugs involve sodium channel blockers such as lidocaine, carbamazepine and mexiletine. Novel drugs such as PF-05089771 and TV-45070 could be promising in ameliorating pain symptoms due to their Nav1.7 selectivity. Patients' symptoms often worsen over time and many patients develop ulcerations and gangrenes caused by excessive exposure to low temperature in order to relieve pain. This review mainly focuses on PE and the causative gene SCN9A--its mutations and their effects on Nav1.7 channels' electrophysiological properties. We propose a genotype-channelopathy-phenotype correlation network underlying PE etiology which could provide guidance for future therapeutics.

The Chinese version of the Yale Food Addiction Scale: An examination of its validation in a sample of female adolescents.

INTRODUCTION: The present study developed and tested a Chinese version of the Yale Food Addiction Scale (YFAS-R-C) in a sample of female normal-school students, with the aim of producing a psychometrically sound tool for assessing food addiction in female adolescents. METHODS: A preliminary study of 72 normal-school students tested the YFAS-R-C and collected suggestions to improve it. Twenty days later, the formal YFAS-R-C, the Binge Eating Scale (BES), Eating Attitude Test (EAT-26), BIS/BAS Reactivity (BIS/BAS) scale, and Regulatory Emotional Self-efficacy (RES) scale were administrated to a sample of 950 normal-school students. Test-retest reliability was assessed in 53 students who took the YFAS-R-C twice. RESULTS: The single factor structure of the YFAS-R-C could be confirmed in our study. The internal consistency (KR-20) for 21 original items (0.857) and diagnostic criteria (0.75) were good. Confirmatory factor analysis verified a one-factor structure with an acceptable fit. The test-retest reliability of the YFAS-R-C was good, with interclass correlations of 0.72 for symptom items and 0.69 for the diagnostic criteria. The YFAS-R-C had good convergent and discriminant validity: symptom and diagnosis versions both had significant correlations with measures of related eating behavior constructs (BES and EAT-26), but had no or moderate correlations with measures of related, yet separate constructs (BIS/BAS and RES). DISCUSSION: The results indicate the YFAS-R-C has a good psychometric validity to differentiate population with and without food addiction in a group of female normal-school students. Future studies should validate the YFAS-R-C in diverse samples.