Annual Progression Rate Research Articles

Natural history of subclinical hypothyroidism and prognostic factors for the development of overt hypothyroidism: Tehran Thyroid Study (TTS).

The significance of subclinical hypothyroidism (SCH) is largely due to its potential risk for developing overt hypothyroidism (OH). Investigations are still exploring predictive factors contributing to the progression of SCH to OH, particularly in patients with mildly elevated serum thyrotropin (TSH). We aimed to clarify the natural history of SCH and the predictive factors of its progression, based on the grade of SCH severity. This study was conducted within the framework of the Tehran Thyroid Study (TTS), in which 5783 individuals aged ≥ 20years were followed. After applying exclusion criteria, data of 270 SCH subjects remained for the analysis. Thyroid function tests were assessed at baseline and every 3years. Of 270 participants with SCH, 239 (88.5%) had TSH level between 5.06 and 10mU/L, and 31 (11.4%) had TSH ≥ 10mU/L. During a median follow-up of 10years, 40% had TSH within the reference range, 44% maintained elevated TSH, and 16% had added low T4 to the elevated TSH. The annual incidence rate of progression to OH was 22.3 (16.5-101.9) per 1000 person-years [18 (12.6-25.6) for those with TSH 5.07-9.9mU/L and 57.8 (22.8-101.9) for patients with TSH ≥ 10mU/L per 1000 person-years (P = 0.001)]. After adjusting age, sex, body mass index (BMI), thyroid peroxidase antibody (TPOAb), and serum TSH, only TPOAb positivity (HR: 2.31; 95% CI 1.10-4.83, P = 0.026) and baseline TSH level ≥ 10mU/L (HR: 5.14; 95% CI 2.14-12.3, P < 0.001) remained as predictors for development of OH. In patients with TSH 5.07-9.9mU/L, TPOAb positivity was associated with an increased risk of OH (HR: 2.41; 95% CI 1.10-5.30, P = 0.027). However, in patients with TSH ≥ 10mU/L, TPOAb positivity was not a predictor (P = 0.49). TPOAb and not TSH are associated with the development of OH in individuals with serum TSH below 10mU/L, and follow-up at regular intervals is recommended in TPOAb-positive individuals with TSH between 5 and 10mU/L.

Determinants of Aortic Stenosis Progression in Bicuspid and Tricuspid Aortic Valves.

Bicuspid aortic valve (BAV) is associated with a faster progression of aortic stenosis (AS). Whether the determinants of AS progression are the same or different in patients with BAV vs tricuspid aortic valve (TAV) is unknown. The aim of this study was to identify the factors associated with the progression of AS in patients with BAV vs patients with TAV. Patients with AS were prospectively recruited in the Metabolic Determinants of the Progression of Aortic Stenosis (PROGRESSA) study (ClinicalTrials.gov Identifier: NCT01679431). The haemodynamic progression rate of AS was assessed by the annualized progression rate of peak aortic jet velocity (Vpeak). Univariable and multivariable linear regression analyses were used to identify the factors associated with a faster progression of AS in patients with BAV vs patients with TAV. There were 79 patients with BAV and 208 patients with TAV. The baseline severity of AS was similar between the 2 groups of patients as well as the annualized progression rate of AS. In patients with BAV, obesity (β= 0.25, P= 0.04), diabetes (β= 0.26, P= 0.02), and BAV with right-noncoronary cusp fusion (β= 0.29, P= 0.01) were found to be independently associated with a faster progression of AS, whereas in patients with TAV, AS baseline severity (baseline Vpeak, β= 0.14, P= 0.04) and chronic kidney disease (β= 0.16, P= 0.02) were significantly associated with AS progression. Factors associated with progression rate of AS are different in BAV and TAV. The main factors associated with a faster progression of AS appear to be obesity, diabetes, right-noncoronary cusp fusion in patients with BAV vs chronic kidney disease in patients with TAV.

Prognostic, Diagnostic and Predictive Biomarkers in the Barrett's Oesophagus-Adenocarcinoma Disease Sequence.

Simple SummaryOesophageal adenocarcinoma (OAC) is a type of cancer of the oesophagus (food pipe) which is associated with poor patient outcomes. Barrett’s oesophagus (BO) is a precancerous condition of the oesophagus associated with chronic heartburn. Currently, surveillance programs exist which monitor patients with BO to prevent it from developing into OAC. However, these surveillance programs are expensive and unpleasant for patients. Prognostic biomarkers are signs which could be measured to determine the chance of someone with BO developing OAC, allowing more targeted surveillance. Similarly, diagnostic biomarkers are indicators which could be measured to see if someone has OAC. Developing new diagnostic biomarkers could allow wider population testing. Only a small proportion of patients with OAC respond to treatment before surgery. Predictive biomarkers could be measured to predict whether someone would respond to the treatments, allowing more individualized therapy. This review focuses on potential biomarkers which could improve patient outcomes in BO/OAC.Oesophageal adenocarcinoma (OAC) incidence has increased dramatically in the developed world, yet outcomes remain poor. Extensive endoscopic surveillance programs among patients with Barrett’s oesophagus (BO), the precursor lesion to OAC, have aimed to both prevent the development of OAC via radiofrequency ablation (RFA) and allow earlier detection of disease. However, given the low annual progression rate and the costs of endoscopy/RFA, improvement is needed. Prognostic biomarkers to stratify BO patients based on their likelihood to progress would enable a more targeted approach to surveillance and RFA of high-risk precursor lesions, improving the cost–risk–benefit ratio. Similarly, diagnostic biomarkers for OAC could enable earlier diagnosis of disease by allowing broader population screening. Current standard treatment for locally advanced OAC includes neoadjuvant chemotherapy (+/− radiotherapy) despite only a minority of patients benefiting from neoadjuvant treatment. Accordingly, biomarkers predictive of response to neoadjuvant therapy could improve patient outcomes by reducing time to surgery and unnecessary toxicity for the patients who would have received no benefit from the therapy. In this mini-review, we will discuss the emerging biomarkers which promise to dramatically improve patient outcomes along the BO-OAC disease sequence.

Differential Temporal Dynamics of Axial and Appendicular Ataxia in SCA3.

BackgroundDisease severity in spinocerebellar ataxia type 3 (SCA3) is commonly defined by the Scale for the Assessment and Rating of Ataxia (SARA) sum score, but little is known about the contributions and progression patterns of individual items.ObjectivesTo investigate the temporal dynamics of SARA item scores in SCA3 patients and evaluate if clinical and demographic factors are differentially associated with evolution of axial and appendicular ataxia.MethodsIn a prospective, multinational cohort study involving 11 European and 2 US sites, SARA scores were determined longitudinally in 223 SCA3 patients with a follow‐up assessment after 1 year.ResultsAn increase in SARA score from 10 to 20 points was mainly driven by axial and speech items, with a markedly smaller contribution of appendicular items. Finger chase and nose‐finger test scores not only showed the lowest variability at baseline, but also the least deterioration at follow‐up. Compared with the full set of SARA items, omission of both tests would result in lower sample size requirements for therapeutic trials. Sex was associated with change in SARA sum score and appendicular, but not axial, subscore, with a significantly faster progression in men. Despite considerable interindividual variability, the average annual progression rate of SARA score was approximately three times higher in subjects with a disease duration over 10 years than in those within 10 years from onset.ConclusionOur findings provide evidence for a difference in temporal dynamics between axial and appendicular ataxia in SCA3 patients, which will help inform the design of clinical trials and development of new (etiology‐specific) outcome measures. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Natural History of Spinocerebellar Ataxia Type 3 in Mainland China: A 2-Year Cohort Study.

ObjectiveThe natural history of spinocerebellar ataxia type 3 (SCA3) has been reported in several populations and shows heterogeneity in progression rate and affecting factors. However, it remains unexplored in the population of Mainland China. This study aimed to identify the disease progression rate and its potential affecting factors in patients with SCA3 in Mainland China.Participants and MethodsWe enrolled patients with genetically confirmed SCA3 in Mainland China. Patients were seen at three visits, i.e., baseline, 1 year, and 2 years. The primary outcome was the Scale for the Assessment and Rating of Ataxia (SARA), and the secondary outcomes were the Inventory of Non-Ataxia Signs (INAS) as well as the SCA Functional Index (SCAFI).ResultsBetween 1 October 2015, and 30 September 2016, we enrolled 263 patients with SCA3. We analyzed 247 patients with at least one follow-up visit. The annual progression rate of SARA was 1.49 points per year (SE 0.08, 95% confidence interval [CI] 1.33–1.65, p < 0.0001). The annual progression rates of INAS and SCAFI were 0.56 points per year (SE 0.05, 95% CI 0.47–0.66, p < 0.001) and −0.30 points per year (SE 0.01, 95% CI −0.33∼-0.28, p < 0.001), respectively. Faster progression in SARA was associated with longer length of the expanded allele of ATXN3 (p < 0.0001); faster progression in INAS was associated with lower INAS at baseline (p < 0.0001); faster decline in SCAFI was associated with shorter length of the normal allele of ATXN3 (p = 0.036) and higher SCAFI at baseline (p < 0.0001).ConclusionOur results provide quantitative data on the disease progression of patients with SCA3 in Mainland China and its corresponding affecting factors, which could facilitate the sample size calculation and patient stratification in future clinical trials.Trial RegistrationThis study was registered with Chictr.org on 15 September 2015, number ChiCTR-OOC-15007124.

Intima-media Thickness Measured at the Common-carotid Artery in Patients Treated with Lipoprotein Apheresis

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Common carotid intima-thickness (CIMT) is as a marker of arterial wall injury and arteriosclerosis. Healthy asymptomatic young and middle-aged individuals of the European-ancestry show mean CIMT of 610 + /-110μmmicrometers with a strong linear relation between age and CIMT. In the general population, an annual rate of change in mean common CIMT is estimated at 15μm (95% CI, 12 to 17), with a median standard deviation of 53. <h3>Objective/Purpose</h3> We sought to compare annual CIMT progression rates in 10 patients with severe hypercholesterolemia treated with lipoprotein apheresis with published annual CIMT progression estimates in age-comparable 1) healthy individuals based on the nomograms, 2) patients with elevated lipoprotein(a), and 3) familial hypercholesterolemia (FH). <h3>Methods</h3> Patients (mean age 60+/-9 years, 70% female, 80% statin intolerant) were treated with the dextran sulfate adsorption apheresis system for primary and secondary atherosclerotic cardiovascular disease (ASCVD) prevention every two weeks between 2005 and 2020 (mean duration, 10+/-4 years). To minimize intra-individual and inter-individual variability in CIMT assessment we used computerized algorithms with measurements performed by the same sonographer. <h3>Results</h3> The baseline mean CIMT was 850+/-170μm and maximum CIMT was 1040+/-220um across the age range of 46 to 70 years. The baseline median levels of total cholesterol were 317 (interquartile range (IQR), 262 to 361); LDL-C, 214 (133 to 253); HDL-C, 56 (44 to 68); triglycerides, 170 (121 to 215), lipoprotein(a), 26 (9 to 120), all in mg/dL. Acute effects of lipoprotein apheresis determined as a difference before and immediately after the procedure were estimated as a median of 72+/-8% and 75+/-7% reduction in the LDL-C and lipoprotein(a) levels, respectively. Regular treatment with lipoprotein apheresis resulted in average reduction in the mean CIMT of −40μm (IQR, −50 to 20). An annual CIMT progression rate was associated with the combined percentage reduction in the lipoprotein(a) (P=0.032) and LDL-C levels (P=0.029). Using the Bayesian Estimation Supersedes the t -Test (BEST) method, the annual rate of CIMT progression was compared to those reported in the literature (Table 1). <h3>Conclusions</h3> Composite CIMT progression rates were slowed with lipoprotein apheresis. In this cohort of high-risk patients with poor statin tolerance, the use of CIMT surveillance was noted to increase compliance with long-term lipid-modifying therapies in the clinical setting.

Plasma cell dyscrasias with complete loss of immunoglobulin heavy chain expression: A rare case

Background: We are presenting a cases of the monoclonal plasma cell proliferative disorders with complete loss of immunoglobulin heavy chain (HC) expression, which is not LC-MGUS. Method: Many literatures and text books were being reviewd regarding the classification, presentation and annual progression rate of Light chain myeloma and other dyscrasias expressing only light chain.Result: Literature data is very scarce. Most of the literatures are batting around LC-MGUS, but not beyond that. Conclusions: More light should be thrown on this darker area of light chain expressing plasma cell dyscrasias for better management.

Prediabetes diagnosis is associated with the progression of coronary artery calcification: The Kangbuk Samsung Health Study.

To investigate the associations between prediabetes defined by different diagnostic criteria and coronary artery calcification (CAC) and its progression over time. This cross-sectional study included 146 436 Korean adults without diabetes who underwent CAC estimation computed tomography (CT) during health examinations from 2011 to 2019. We used multinomial logistic regression models. The longitudinal study comprised 41 100 participants with at least one follow-up cardiac CT and annual CAC progression rates and ratios were estimated. Prediabetes was categorized into three groups: isolated glucose prediabetes (fasting blood glucose [FBG] 100-125 mg/dl, HbA1c < 5.7%), isolated HbA1c prediabetes (FBG < 100 mg/dl, HbA1c 5.7%-6.4%) and prediabetes meeting both FBG and HbA1c criteria (FBG 100-125 mg/dl, HbA1c 5.7%-6.4%). After adjusting for covariates, the prevalence ratios (95% CI) for CAC scores of more than 100 comparing isolated glucose prediabetes, isolated HbA1c prediabetes and prediabetes fulfilling both criteria with those of normoglycaemia were 1.12 (0.99-1.26), 1.24 (1.11-1.39) and 1.31 (1.18-1.45), respectively. The multivariable-adjusted ratio (CIs) of annual CAC progression rates comparing the corresponding groups with the normoglycaemia group were 1.031 (1.023-1.039), 1.025 (1.019-1.032) and 1.054 (1.047-1.062), respectively. CAC risk and CAC progression were consistently highest in individuals meeting both glucose and HbA1c criteria, while all three prediabetes types showed a significantly increased risk of CAC progression. Atherosclerosis risk reduction management is necessary for prediabetes, especially in patients meeting both criteria.

The role of dendrin in IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) and its systemic variant IgA vasculitis (IgAV) damage the glomeruli, resulting in proteinuria, hematuria and kidney impairment. Dendrin is a podocyte-specific protein suggested to be involved in the pathogenesis of IgAN. Upon cell injury, dendrin translocates from the slit diaphragm to the nucleus, where it is suggested to induce apoptosis and cytoskeletal changes, resulting in proteinuria and accelerated disease progression in mice. Here we investigated gene and protein expression of dendrin in relation to clinical and histopathological findings to further elucidate its role in IgAN/IgAV. Glomerular gene expression was measured using microarray on 30 IgAN/IgAV patients, 5 patients with membranous nephropathy (MN) and 20 deceased kidney donors. Dendrin was spatially evaluated on kidney tissue sections by immunofluorescence (IF) staining (IgAN patients, n=4; nephrectomized kidneys, n=3) and semi-quantified by immunogold electron microscopy (IgAN/IgAV patients, n=21; MN, n=5; living kidney donors, n=6). Histopathological grading was performed according to the Oxford and Banff classifications. Clinical data were collected at the time of biopsy and follow-up. Dendrin mRNA levels were higher (P=.01) in IgAN patients compared with MN patients and controls and most prominently in patients with preserved kidney function and fewer chronic histopathological changes. Whereas IF staining did not differ between groups, immunoelectron microscopy revealed that a higher relative nuclear dendrin concentration in IgAN patients was associated with a slower annual progression rate and milder histopathological changes. Dendrin messenger RNA levels and relative nuclear protein concentrations are increased and associated with a more benign phenotype and progression in IgAN/IgAV patients.

Predicting the 2-Year Risk of Progression from Prediabetes to Diabetes Using Machine Learning among Chinese Elderly Adults.

Identifying people with a high risk of developing diabetes among those with prediabetes may facilitate the implementation of a targeted lifestyle and pharmacological interventions. We aimed to establish machine learning models based on demographic and clinical characteristics to predict the risk of incident diabetes. We used data from the free medical examination service project for elderly people who were 65 years or older to develop logistic regression (LR), decision tree (DT), random forest (RF), and extreme gradient boosting (XGBoost) machine learning models for the follow-up results of 2019 and 2020 and performed internal validation. The receiver operating characteristic (ROC), sensitivity, specificity, accuracy, and F1 score were used to select the model with better performance. The average annual progression rate to diabetes in prediabetic elderly people was 14.21%. Each model was trained using eight features and one outcome variable from 9607 prediabetic individuals, and the performance of the models was assessed in 2402 prediabetes patients. The predictive ability of four models in the first year was better than in the second year. The XGBoost model performed relatively efficiently (ROC: 0.6742 for 2019 and 0.6707 for 2020). We established and compared four machine learning models to predict the risk of progression from prediabetes to diabetes. Although there was little difference in the performance of the four models, the XGBoost model had a relatively good ROC value, which might perform well in future exploration in this field.

PB1965: A META-ANALYSIS OF THE RATE OF MALIGNANT PROGRESSION OF MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE: PRELIMINARY FINDINGS FROM A SYSTEMATIC REVIEW

Background: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant condition preceding multiple myeloma (MM) and other haematological malignancies (HM). Clinically the rate of progression from MGUS to HM is important; current guidelines from the International Myeloma Working Group (IMWG) report this rate as “around 1% per year”, however variation has been reported by ethnic groups, MGUS type, and clinical features. Aims: A systematic review of the published literature was conducted to investigate the rate of MGUS progression to support clinical practice. Methods: Four electronic databases (Embase, Medline, Pubmed and Web of Science) were searched from database inception to 11/12/2019 using key words and MeSH subject headings for “MGUS”, “haematological malignancy” and “progression”. Studies were reviewed against predefined eligibility criteria by two independent reviewers. For studies reporting progression events and person-years of follow-up, a random-effects meta-analysis model5 was used to produce a pooled rate of MGUS progression to HM and MM. Studies reporting on cumulative rates of progression at specified time-points (1, 5 and 10-year) were included in a narrative synthesis. Results: Overall, 36 papers met the inclusion criteria; 12 studies (sample size: 114-17,963; follow-up 3.3-42.1 years) were included in the meta-analysis. In preliminary analyses, the annual pooled rate of MGUS progression was 1.1% (95%CI 0.9-1.3) to HM and 0.9% (95%CI 0.7-1.1) to MM. In total, 18 studies contributed to the narrative synthesis on MGUS progression to HM (sample size: 52-17,963; follow-up 2.1-34.1 years) and 10 studies reported on MGUS progression to MM (sample size: 75-2046, follow-up: 2.1-17 years). These narrative syntheses highlighted the heterogeneity of research, which encompassed key traits like methods, sample sizes and follow-up duration. Studies were also mainly conducted in Europe, being particularly scarce in Asia. Between meta-analysis and narrative synthesis, only seven studies reported on IgM-MGUS progression to Waldenström’s macroglobinaemia or HM, which could not be clearly synthesised in either analysis due to differing reporting; these papers indicated higher progression rates in IgM-MGUS than non-IgM. Summary/Conclusion: Preliminary findings from this systematic review support current IMWG guidelines on the rate of MGUS progression to HM. However, as the majority of studies included were limited to geographic areas within Europe and USA, further research reflecting population and clinical diversity are needed.

A Clinical and Epidemiological Prevalence Study on Friedreich’s Ataxia in Latium, Italy

Objective: The aim of this study was to estimate the Friedreich’s ataxia (FRDA) prevalence in a highly populated region of Italy (previous studies in small geographic areas gave a largely variable prevalence) and to define the patients’ molecular and clinical characteristics. Methods: For the point-prevalence study, we considered patients belonging to families with a molecular diagnosis of FRDA and resident in Latium on 1 January 2019. The crude prevalence of FRDA, specific for age and sex, was calculated and standardized for age using the Italian population. Moreover, we investigated possible correlations among patients’ genetic profile, symptoms, and age of onset. Results: We identified 63 FRDA patients; the crude prevalence for total, males, and females were 1.07 (95% CI: 0.81–1.37), 0.81 (95% CI: 0.54–1.22), and 1.32 (95% CI: 0.97–1.79), per 100,000 inhabitants. We divided FRDA patients by three age-at-onset groups (early-EOFA 73%; late-LOFA 11.1%; very late-VLOFA 15.9%) and found significant differences in the scale for the assessment and rating of ataxia (SARA; p = 0.001), a biased distribution of the shorter allele (p = 0.001), an excess of scoliosis and cardiomyopathy (p = 0.001) in EOFA. To determine the contribution of patients’ molecular and clinical characteristics to the annual rate of progression, we performed a multivariate regression analysis that gave an R² value of 45.3%. Conclusions: We estimated the crude and standardized prevalence of FRDA in Latium. A clinical classification (EOFA, LOFA, VLOFA) gave significant correlations. This epidemiological estimate allows monitoring disease prevalence over time in cohort studies and/or for developing disease registry.

MO412: Impact of Body Mass Index on Mortality and End–Stage Kidney Disease in Patients With Non-Dialysis Dependent Chronic Kidney Disease

Abstract BACKGROUND AND AIMS Obesity is a major global problem affecting more than 1.9 billion adults [1]. The aetiological factors of obesity are complex and consist of genetic, social and environmental elements. Obesity can lead to chronic kidney disease (CKD) via both direct and indirect pathways. However, the effect of obesity on the progression of CKD remains unclear. This study aimed to investigate the impact of higher body mass index (BMI) on clinical outcomes in a large UK cohort of patients with non-dialysis dependent (NDD)-CKD. METHOD The Salford Kidney Study is a longitudinal prospective cohort of more than 3000 patients with NDD-CKD. All patients with available BMI at baseline from October 2002 to December 2016 were included in this study. Patients were grouped according to their BMI into underweight [(BMI &amp;lt; 18.5 kg/m2), n = 35], healthy weight [(BMI 18.5–24.9 kg/m2), n = 628], overweight [(BMI 25–29.9 kg/m2), n = 860] and obese [(BMI &amp;gt; 30 kg/m2), n = 897]. Cox-regression analysis was performed to study the strength of association between BMI groups and major clinical outcomes [all-cause mortality, end-stage kidney disease (ESKD) and annual rate of progression of CKD (delta eGFR)] by using the healthy weight BMI group as a reference. The outcomes were also analysed in a 1:1 propensity score-matched analysis between patients in the healthy weight and obese groups (414 in each). RESULTS A total of 2420 patients with a median follow-up of 44.3 months were available for analysis. The median age of the cohort was 67 years and 58% were male. The prevalence of hypertension and diabetes increased with a higher BMI (84.0% and 18.8% in healthy weight, 91.7% and 31.0% in overweight and 94.2% and 46.8% in the obese groups, respectively). There was no significant difference in the baseline eGFR between the groups with a median of 29.3 mL/min/1.73 m2. There was an inverse association between a higher BMI and all-cause mortality [obese versus healthy weight: hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.81–0.96; P = 0.004] but there was no association observed with ESKD (HR 0.96; 95% CI: 0.87–1.06; P = 0.422). The delta eGFR was not significantly different between the different BMI groups (Table 1). A similar observation with all-cause mortality being better in the obese group was noted in the propensity-matched analysis (HR:0.88; CI:0.81–0.96; P = 0.004) (Table 2). CONCLUSION In our large cohort of patients, a higher BMI was seen to be protective against all-cause mortality. Furthermore, the annual rate of decline in eGFR was similar among the BMI groups. Patients with normal BMI had significantly higher all-cause mortality compared with the obese group.

Progression to Dementia or Reversion to Normal Cognition in Mild Cognitive Impairment as a Function of Late-Onset Neuropsychiatric Symptoms.

Background and ObjectivesMild cognitive impairment (MCI) is an at-risk state for dementia; however, not all individuals with MCI transition to dementia, and some revert to normal cognition (NC). Here, we investigate whether mild behavioral impairment (MBI), the late-life onset of persistent neuropsychiatric symptoms (NPS), improves the prognostic specificity of MCI.MethodsParticipants with MCI from the National Alzheimer's Coordinating Center Uniform Data Set were included. NPS were operationalized with the Neuropsychiatric Inventory Questionnaire to identify participants without NPS and those with MBI (persistent, late-onset NPS). Individuals with late-onset NPS not meeting the MBI persistence criterion (NPS_NOT_MBI) were retained for secondary analyses. Progression to dementia, stable MCI, and reversion to NC after 3 years of follow-up were defined per National Institute on Aging–Alzheimer’s Association and Petersen criteria.ResultsThe primary sample consisted of 739 participants (NPS− n = 409 and MBI+ n = 330; 75.16 ± 8.6 years old, 40.5% female). After 3 years, 238 participants (33.6%) progressed to dementia, and 90 (12.2%) reverted to NC. Compared to participants without NPS, participants with MBI were significantly more likely to progress to dementia (adjusted odds ratio [AOR] 2.13, 95% CI 1.52–2.99), with an annual progression rate of 14.7% (vs 8.3% for participants with MCI without NPS). Compared to participants without NPS, participants with MBI were less likely to revert to NC (AOR 0.48, 95% CI 0.28–0.83, 2.5% vs 5.3% annual reversion rate). The NPS_NOT_MBI group (n = 331, 76.5 ± 8.6 years old, 45.9% female) were more likely to progress to dementia (AOR 2.18, 95% CI 1.56–3.03, 14.3% annual progression rate) but not less likely to revert to NC than those without NPS. Accordingly, both NPS_NOT_MBI and MBI+ participants had lower Mini-Mental State Examination scores than NPS− participants after 3 years.DiscussionLate-onset NPS improve the specificity of MCI as an at-risk state for progression to dementia. However, only persistent late-onset NPS are associated with a lower likelihood of reversion to NC, with transient NPS (i.e., NPS_NOT_MBI) not differing from the NPS− group. Clinical prognostication can be improved by incorporating late-onset NPS, especially those that persist (i.e., MBI), into risk assessments. Clinical trials may benefit from enrichment with these higher-risk participants with MCI.

Effect of menopausal hormone therapy on arterial wall echomorphology: Results from the Early versus Late Intervention Trial with Estradiol (ELITE)

ObjectiveTo evaluate the effect of hormone therapy (HT) on arterial wall composition by ultrasound. BackgroundThe effect of HT on the progression of subclinical atherosclerosis has been well-described using measurements of common carotid artery (CCA) wall thickness. However, it is unknown whether the change in arterial wall anatomic structure is accompanied by an effect of HT on arterial wall composition. MethodsA total of 643 healthy postmenopausal women divided into two strata according to the time since menopause (<6 years, the early-postmenopause group; or >10 years, the late-postmenopause group) were randomized to receive either active treatment or placebo. For hysterectomized women, the active treatment was oral micronized 17β-estradiol 1 mg/day; for women with a uterus, 4% vaginal micronized progesterone gel 45 mg/day for 10 days each month was added to the estradiol regimen. Gray-scale median of the CCA intima-media complex (IM-GSM), a (unitless) measurement of arterial wall composition based on echogenicity, was determined by high-resolution B-mode ultrasonography. Lower IM-GSM, or less echogenicity, indicates more atherosclerosis. IM-GSM and serum estradiol (E2) concentration were assessed every 6 months over a median 4.8-year trial period. Linear mixed effects regression models were used for all analyses. ResultsOverall, IM-GSM progression/year had a negative trajectory, reflecting reduction in echogenicity over time (worsening atherosclerosis). HT effects on IM-GSM progression/year differed by postmenopause strata (interaction p-value = 0.02). IM-GSM progression/year (95% CI) in the early postmenopause group randomized to HT was −0.50 (−0.82, −0.18)/year compared with −1.47 (−1.81, −1.13)/year among those randomized to placebo (p-value <0.0001). In the late postmenopause group, the annual IM-GSM progression rate did not significantly differ between HT and placebo (p = 0.28). Higher mean on-trial E2 (pg/ml) levels were associated with higher IM-GSM progression, indicating less atherosclerosis progression in all women (β (95% CI) = 0.006 (0.0003, 0.01), p = 0.04). For each pg/dl E2, IM-GSM progression/year was 0.007 ((−0.0002, 0.01), p = 0.056) in the early and 0.003 ((−0.006, 0.01), p = 0.50) in the late postmenopause group (interaction p-value = 0.51). CIMT progression rate (μm/year) was significantly inversely associated with the IM-GSM progression (β (95% CI) = −4.63 (−5.6, −3.7), p < 0.001). ConclusionsHT, primarily with oral estradiol, reduced atherogenic progression of arterial wall composition in healthy postmenopausal women who were within 6 years from menopause.Trial registration number: NCT01553084

Cost-Effectiveness of Dapagliflozin for Non-diabetic Chronic Kidney Disease.

In the USA, chronic kidney disease (CKD) affects 1 in 7 adults and costs $100 billion annually. The DAPA-CKD trial found dapagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, to be effective in reducing CKD progression and mortality in patients with diabetic and non-diabetic CKD. Currently, SGLT2 inhibitors are not considered standard of care for patients with non-diabetic CKD. Determine the cost-effectiveness of adding dapagliflozin to standard management of patients with non-diabetic CKD. Markov model with lifetime time horizon and US healthcare sector perspective. Patients with non-diabetic CKD INTERVENTION: Dapagliflozin plus standard care versus standard care only. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs), all discounted at 3% annually; total incidence of kidney failure on kidney replacement therapy; average years on kidney replacement therapy. Adding dapagliflozin to standard care improved life expectancy by 2 years, increased discounted QALYS (from 6.75 to 8.06), and reduced the total incidence of kidney failure on kidney replacement therapy (KRT) (from 17.4 to 11.0%) and average years on KRT (from 0.77 to 0.43) over the lifetime of the cohort. Dapagliflozin plus standard care was more effective than standard care alone while increasing lifetime costs (from $245,900 to $324,8900, or $60,000 per QALY gained). Results were robust to variations in assumptions about dapagliflozin's efficacy over time and by CKD stage, added costs of kidney replacement therapy, and expected population annual CKD progression rates and sensitive to the cost of dapagliflozin. The net 1-year budgetary implication of treating all US patients with non-diabetic CKD could be up to $21 billion. Dapagliflozin improved life expectancy and reduced progression of CKD, the proportion of patients requiring kidney replacement therapy, and time on kidney replacement therapy in patients with non-diabetic CKD. Use of dapagliflozin meets conventional criteria for cost-effectiveness.

Time spent outdoors as an intervention for myopia prevention and control in children: an overview of systematic reviews.

PurposeOutdoor light exposure is considered a safe and effective strategy to reduce myopia development and aligns with existing public health initiatives to promote healthier lifestyles in children. However, it is unclear whether this strategy reduces myopia progression in eyes that are already myopic. This study aims to conduct an overview of systematic reviews (SRs) reporting time spent outdoors as a strategy to prevent myopia or slow its progression in children.MethodsWe searched the Cochrane Library, EMBASE, MEDLINE and CINAHL from inception to 1 November 2020 to identify SRs that evaluated the association between outdoor light exposure and myopia development or progression in children. Outcomes included incident myopia, prevalent myopia and change in spherical equivalent refraction (SER) and axial length (AL) to evaluate annual rates of myopia progression. The methodological quality and risk of bias of included SRs were assessed using the AMSTAR‐2 and ROBIS tools, respectively.ResultsSeven SRs were identified, which included data from 47 primary studies with 63,920 participants. Pooled estimates (risk or odds ratios) consistently demonstrated that time outdoors was associated with a reduction in prevalence and incidence of myopia. In terms of slowing progression in eyes that were already myopic, the reported annual reductions in SER and AL from baseline were small (0.13–0.17 D) and regarded as clinically insignificant. Methodological quality assessment using AMSTAR‐2 found that all reviews had one or more critical flaws and the ROBIS tool identified a low risk of bias in only two of the included SRs.ConclusionThis overview found that increased exposure to outdoor light reduces myopia development. However, based on annual change in SER and AL, there is insufficient evidence for a clinically significant effect on myopia progression. The poor methodological quality and inconsistent reporting of the included systematic reviews reduce confidence in the estimates of effect.

Intensive Postural and Motor Activity Program Reduces Scoliosis Progression in People with Rett Syndrome.

Background: A scoliosis prevalence of 94% was reported in the population with Rett syndrome (RTT), with an annual progression rate of 14 to 21° Cobb which may result in pain, loss of sitting balance, deterioration of motor skills, and lung disfunction. This paper describes the efficacy of an intensive conservative individualized physical and postural activity program in preventing scoliosis curvature progression in patients with RTT. Methods: Twenty subjects diagnosed with RTT and scoliosis were recruited, and an individualized intensive daily physical activity program was developed for each participant. Each program was conducted for six months by participants’ primary caregivers in their daily living environment. Fortnightly remote supervision of the program implementation was provided by an expert therapist. Pre- and post-intervention radiographs and motor functioning were analyzed. Results: An averaged progression of +1.7° ± 8.7° Cobb, over one year (12.3 ± 3.5 months) was observed in our group, together with motor function improvements. A relation between curve progression and motor skill improvement was observed. Conclusions: The intervention prevented scoliosis progression in our group. The achievement of functional motor improvements could enable better body segment control and muscle balancing, with a protective effect on scoliosis progression. The intervention was effective for individuals with RTT across various ages and severity levels. Individual characteristics of each participant and the details of their activity program are described.

Annual Incidences and Progressions of Myopia and High Myopia in Chinese Schoolchildren Based on a 5-Year Cohort Study.

PurposeTo determine the annual incidences and rates of progression of myopia and high myopia in Chinese schoolchildren from grade 1 to grade 6 and explore the possible cause-specific risk factors for myopia.MethodsFrom 11 randomly selected primary schools in Anyang city, central China, 2835 grade 1 students were examined with annual follow ups for 5 years. Students were invited to undergo a comprehensive examination, including cycloplegic autorefraction, ocular biometry, and standardized questionnaires.ResultsThe mean spherical equivalent refraction decreased substantially from +0.94 ± 1.03 diopter (D) in grade 1 to −1.37 ± 2.08 D in grade 6, with rapid annual myopic shifts, especially for students in grades 3 through 6 (−0.51 to −0.59 D). The prevalence of myopia increased substantially, with the yearly incidence of myopia increasing from 7.8% in grade 1 and 2 to 25.3% in grades 5 and 6, and the incidence of high myopia increased from 0.1% to 1.0%. The 5-year incidence of myopia was lowest among children who has a baseline spherical equivalent refraction of greater than +2.00 D (4.4%), and increased to nearly 92.0% among children whose baseline spherical equivalent refraction was 0.00 to −0.50 D. The incidence of myopia was higher in children who had less hyperopic baseline refraction, two myopic parents, longer axial length, deeper anterior chamber, higher axial length–corneal radius of curvature ratio, and thinner lenses.ConclusionsBoth the annual incidence and progression rates of myopia and high myopia were high in Chinese schoolchildren, especially after grade 3. Hyperopic refraction of children should be monitored before primary school as hyperopia reserve to prevent the onset of myopia and high myopia.

Impact of online classes and home confinement on myopia progression in children during COVID-19 pandemic: Digital eye strain among kids (DESK) study 4.

Purpose:This study was performed to compare the rate of progression of myopia before and during the COVID-19 pandemic and to assess the risk factors of hastened progression.Methods:All children with myopia of spherical equivalence ≤ −0.5 D with at least two prior documented refractions 6 months and 1 year before were included. The annual progression rate before COVID-19 and during COVID-19 was calculated. Annual myopia progression was categorized as no progression (0), slow progression (<1 D), and fast progression (≥1 D).Results:A total of 133 children (266 eyes) aged 6–18 years were included in the study. Mean annual myopia progression was found to be statistically significant during COVID-19 as compared with pre-COVID-19 (0.90 vs 0.25 D, P < 0.00001). A total of 45.9% of children showed an annual progression of ≥1 D during the pandemic as compared with 10.5% before the COVID-19 (p < 0.00001). In multivariate analysis, history of rapid progression in pre-COVID-19 era (P = 0.002) and sun exposure <1 h/day (P < 0.00001) were found to be independent risk factors for rapid myopia progression.Conclusion:Parents should consider risk of rapid myopia progression in children during current pandemic and children should be provided with socially distant outdoor activities to increase their sun exposure and diminish the rate of myopia progression.