Estimates Of Progression Rates Research Articles

Disease Progression and Multiparametric Imaging Characteristics of Spinocerebellar Ataxia Type 3 With Spastic Paraplegia.

Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia that occurs worldwide. Clinical patterns were observed, including the one characterized by marked spastic paraplegia. This study investigated the clinical features, disease progression, and multiparametric imaging aspects of patients with SCA3. We retrospectively analyzed 249 patients with SCA3 recruited from the Organization for Southeast China for cerebellar ataxia research between October 2014 and December 2020. Of the 249 patients, 145 were selected and assigned to 2 groups based on neurologic examination: SCA3 patients with spastic paraplegia (SCA3-SP) and SCA3 patients with nonspastic paraplegia (SCA3-NSP). Participants underwent 3.0-T brain MRI examinations, and voxel-wise and volume-of-interest-based approaches were used for the resulting images. A tract-based spatial statistical approach was used to investigate the white matter (WM) alterations using diffusion tensor imaging, neurite orientation dispersion, and density imaging metrics. Multiple linear regression analyses were performed to compare the clinical and imaging parameters between the 2 groups. The longitudinal data were evaluated using a linear mixed-effects model. Forty-three patients with SCA3-SP (mean age, 37.58years ± 11.72 [SD]; 18 women) and 102 patients with SCA3-NSP (mean age, 47.42years ± 12.50 [SD]; 39 women) were analyzed. Patients with SCA3-SP were younger and had a lower onset age but a larger cytosine-adenine-guanine repeat number, as well as higher clinical severity scores (all corrected p < 0.05). The estimated progression rates of the Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale scores were higher in the SCA3-SP subgroup than in the SCA3-NSP subgroup (SARA, 2.136 vs 1.218 points; ICARS, 5.576 vs 3.480 points; both p < 0.001). In addition, patients with SCA3-SP showed gray matter volume loss in the precentral gyrus with a decreased neurite density index in the WM of the corticospinal tract and cerebellar peduncles compared with patients with SCA3-NSP. SCA3-SP differs from SCA3-NSP in clinical features, multiparametric brain imaging findings, and longitudinal follow-up progression.

Cost-effectiveness of chimeric antigen receptor T-cell therapy in adults with relapsed or refractory follicular lymphoma.

Follicular lymphoma (FL) is traditionally considered treatable but incurable. In March 2021, the US Food and Drug Administration approved the use of chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory (R/R) FL after ≥2 lines of therapy. Priced at $373 000, CAR T-cell therapy is potentially curative, and its cost-effectiveness compared with other modern R/R FL treatment strategies is unknown. We developed a Markov model to assess the cost-effectiveness of third-line CAR T-cell vs standard of care (SOC) therapies in adults with R/R FL. We estimated progression rates for patients receiving CAR T-cell and SOC therapies from the ZUMA-5 trial and the LEO CReWE study, respectively. We calculated costs, discounted life years, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) of CAR T-cell vs SOC therapies with a willingness-to-pay threshold of $150 000 per QALY. Our analysis was conducted from a US payer's perspective over a lifetime horizon. In our base-case model, the cost of the CAR T-cell strategy was $731 682 compared with $458 490 for SOC therapies. However, CAR T-cell therapy was associated with incremental clinical benefit of 1.50 QALYs, resulting in an ICER of $182 127 per QALY. Our model was most sensitive to the utilities associated with CAR T-cell therapy remission and third-line SOC therapies and to the total upfront CAR T-cell therapy cost. Under current pricing, CAR T-cell therapy is unlikely to be cost-effective in unselected patients with FL in the third-line setting. Both randomized clinical trials and longer term clinical follow-up can help clarify the benefits of CAR T-cell therapy and optimal sequencing in patients with FL.

Neuroprotective Trials in REM Sleep Behavior Disorder: The Way Forward Becomes Clearer.

As neuroprotective therapies continue to be advanced against neurodegenerative synucleinopathies, such as Parkinson disease (PD), dementia with Lewy bodies (DLBs), and multiple system atrophy, increasing attention is turning to the prodromal stages of disease. Treatments at the prodromal stage have the compelling advantages of being applied early enough to make a meaningful difference and can be tested without confounding by symptomatic therapies used for clinical PD/DLB. As it currently stands, patients with idiopathic/isolated REM sleep behavior disorder (iRBD) represent the only large existing cohort of untreated prodromal PD/DLB that would be ready to start a clinical trial now. Several thousand patients with RBD are currently being followed in research-based clinics, and more than 80% of them will develop a full neurodegenerative synucleinopathy. Research into RBD phenoconversion rates and predictors has advanced considerably, and we are now able to generate increasingly precise estimates of progression rates, can select stratification markers to enrich trials, and are able to understand the progression and sample size implications of different primary outcome measures. This review will outline the potential for neuroprotective trials in iRBD, including the pathophysiologic mechanisms with the most promise to target in iRBD, selection criteria for inclusion, and the optimal primary trial outcome measures to choose.

Dissecting the Domains of Parkinson's Disease: Insights from Longitudinal Item Response Theory Modeling.

Longitudinal item response theory (IRT) models previously suggested that the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor examination has two salient domains, tremor and nontremor, that progress in time and in response to treatment differently. Apply longitudinal IRT modeling, separating tremor and nontremor domains, to reanalyze outcomes in the previously published clinical trial (Study of Urate Elevation in Parkinson's Disease, Phase 3) that showed no overall treatment effects. We applied unidimensional and multidimensional longitudinal IRT models to MDS-UPDRS motor examination items in 298 participants with Parkinson's disease from the Study of Urate Elevation in Parkinson's Disease, Phase 3 (placebo vs. inosine) study. We separated 10 tremor items from 23 nontremor items and used Bayesian inference to estimate progression rates and sensitivity to treatment in overall motor severity and tremor and nontremor domains. The progression rate was faster in the tremor domain than the nontremor domain before levodopa treatment. Inosine treatment had no effect on either domain relative to placebo. Levodopa treatment was associated with greater slowing of progression in the tremor domain than the nontremor domain regardless of inosine exposure. Linear patterns of progression were observed. Despite different domain-specific progression patterns, tremor and nontremor severities at baseline and over time were significantly correlated. Longitudinal IRT analysis is a novel statistical method addressing limitations of traditional linear regression approaches. It is particularly useful because it can simultaneously monitor changes in different, but related, domains over time and in response to treatment interventions. We suggest that in neurological diseases with distinct impairment domains, clinical or anatomical, this application may identify patterns of change unappreciated by standard statistical methods. © 2022 International Parkinson and Movement Disorder Society.

Efficacy and safety of photodynamic therapy mediatied by 5-aminolevulinic acid for the treatment of vaginal high-grade intraepithelial lesions

BackgroundVaginal high-grade squamous intraepithelial lesion (HSIL) (vaginal intraepithelial neoplasia [VAIN] grade 2–3) is clinically, a precancerous lesion condition with an estimated progression rate of 10%–20%. Therefore, treatment is recommended. Because traditional treatments have limited effects, high expense and complications, here we evaluated the efficacy and safety of topical 5-aminolevulinic acid (ALA)–based photodynamic therapy (PDT). MethodsThis study consisted of 56 female patients diagnosed with vaginal HSIL. A 20% 5-ALA jelly formation was topically applied to the vaginal wall, followed by 635 nm PDT at 7–14 days intervals. Cytology, human papillomavirus (HPV) genotyping, colposcopy, and pathology were assessed after treatment. ResultsAmong the 56 patients in our study, 47 (83.9%) had VAIN 2 and 9 (16.1%) had VAIN 3. 35 patients underwent three courses of PDT treatment, 19 experienced six courses, and two experienced nine courses. The total pathological regression rate was 87.5%, and the HPV clearance rate during the 6-month follow-up was 41.9%. Lesions located in the vaginal stump after hysterectomy seem to be difficult to treat. 9%(4/44) and 23%(7/30) patients had recurrent disease during the 6-month and 1-year follow-up time point. The most common adverse event was increased vaginal discharge, other side effects include abdominal pain, vulvar pruritus, and vaginal bleeding. No severe adverse effect was observed during the treatment. ConclusionPhotodynamic therapy mediatied by 5-aminolevulinic acid is an effective and safe treatment for vaginal HSIL with minimal side effects.

Diagnostic progression to schizophrenia in 35,255 patients with obsessive-compulsive disorder: a longitudinal follow-up study.

Evidence suggests a continuity between obsessive-compulsive disorder (OCD) and schizophrenia. However, the factors that may predict diagnostic progression from OCD to schizophrenia remain unclear. A total of 35,255 adolescents and adults with OCD (ICD-9-CM code: 300.3) were enrolled between 2001 and 2010 and followed up at the end of 2011 for the identification of de novo schizophrenia (ICD-9-CM code: 295). The Kaplan-Meier method was used to estimate incidence rates, and the Cox regression was used to determine the significance of candidate predictors. At the end of the 11-year follow-up period, the crude cumulative progression rate from OCD to schizophrenia was 6%, and the estimated progression rate totaled 7.80%. Male sex (hazard ratio: 1.23), obesity (1.77), autism spectrum disorder (1.69), bipolar disorder (1.69), posttraumatic stress disorder (1.65), cluster A personality disorder (2.50), and a family history of schizophrenia (2.57) also were related to an elevated likelihood of subsequent progression to schizophrenia in patients with OCD. Further study is necessary to elucidate the exact pathomechanisms underlying diagnostic progression to schizophrenia in patients with OCD.

Determinants of Hyperkalemia Progression Among Patients with Mild Hyperkalemia.

IntroductionThe progression of mild hyperkalemia and the predictors of progression have not been well characterized. In this study we aimed to characterize the progression of hyperkalemia and identify the risk factors for hyperkalemia progression.MethodsAdults with mild hyperkalemia (at least one serum potassium measure > 5.0 and ≤ 5.5 mEq/L) were identified using electronic medical records from the Research Action for Health Network (2012–2018). Progression to moderate-to-severe and progression to severe hyperkalemia were defined as the first occurrences of a serum potassium measure > 5.5 and > 6.0 mEq/L, respectively. Kaplan–Meier analyses were conducted to estimate progression rates for all patients and by pre-specified patient subgroups. Hazard ratios (HR) of moderate-to-severe and severe hyperkalemia progression were estimated using Cox models.ResultsOf 35,369 patients with mild hyperkalemia, 16.9% and 8.7% progressed to moderate-to-severe and severe hyperkalemia, respectively. Rates of hyperkalemia progression elevated with the severity of chronic kidney disease (CKD). The highest progression rates were seen in patients with CKD stage 5 (stage 5 vs. no CKD: moderate-to-severe, 50.2% vs. 12.0%; severe, 31.3% vs. 3.9%; p < 0.001). Higher progression rates were also observed in patients with heart failure, hypertension, and type II diabetes compared with patients without those conditions (all p < 0.001). The most prominent risk factors were CKD stage 5 (HR of progression to moderate-to-severe hyperkalemia, 3.32 [95% CI 3.03–3.64]; severe, 4.08 [3.55–4.69]), CKD stage 4 (2.19 [1.97–2.43], 2.28 [1.92–2.71]), CKD stage 3 (1.57 [1.46–1.68], 1.65 [1.46–1.87]), type I diabetes (1.37 [1.18–1.61], 1.54 [1.23–1.93]), and serum potassium (1.12 [1.10–1.15], 1.13 [1.10–1.17] per 0.1 mEq/L increase) (all p values < 0.05).ConclusionHyperkalemia progression rates increased significantly with CKD stage and were also higher among patients with higher baseline potassium level, heart failure, hypertension, and diabetes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01925-1.

Estimating Progression Rates Across the Spectrum of Alzheimer's Disease for Amyloid-Positive Individuals Using National Alzheimer's Coordinating Center Data.

IntroductionPublished estimates of Alzheimer’s disease (AD) progression do not capture the full disease continuum. This study provides transition probabilities of individuals with amyloid-β (Aβ+) pathology across the disease continuum.MethodsPatient-level longitudinal data from the National Alzheimer’s Coordinating Center were used to estimate progression rates. Progression rates through five clinically defined AD stages—asymptomatic, mild cognitive impairment due to AD (MCI-AD), mild AD dementia, moderate AD dementia, severe AD dementia—and death were measured as transition probabilities. Rates were assessed in “incident” patients who recently entered the stage, controlling for covariates. Transition probabilities were generated from multinomial logit regression models that predicted an individual’s health state as a function of health state at the previous visit and adjusted for time between initial and follow-up visits, age, sex, years of education, and concomitant symptomatic AD medications.ResultsAnnual transition probabilities to more severe dementia stages for surviving incident Aβ+ patients were as follows: asymptomatic to MCI-AD, 40.8%; MCI-AD to mild AD dementia or worse, 21.8%; mild AD dementia to moderate AD dementia or worse, 35.9%; moderate AD dementia to severe AD dementia, 28.6%. Transition probabilities to less severe dementia stages were: 5.3% annual reversion from MCI-AD to asymptomatic, 3.0% mild AD dementia to MCI-AD, 1.8% moderate AD dementia to mild AD dementia, and 1.3% for severe AD dementia to moderate AD dementia.ConclusionsThese transition probabilities reflect the full continuum of AD progression in Aβ+ individuals and can be used to assess the impact of treatment on expected transitions.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00272-1.

A Disease Progression Model to Quantify the Nonmotor Symptoms of Parkinson's Disease in Participants With Leucine-Rich Repeat Kinase 2 Mutation.

Leucine-rich repeat kinase 2 (LRRK2) inhibitors are currently in clinical development as interventions to slow progression of Parkinson's disease (PD). Understanding the rate of progression in PD as measured by both motor and nonmotor features is particularly important in assessing the potential therapeutic effect of LRRK2 inhibitors in clinical development. Using standardized data from the Critical Path for Parkinson's Unified Clinical Database, we quantified the rate of progression of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I (nonmotor aspects of experiences of daily living) in 158 participants with PD who were carriers and 598 participants with PD who were noncarriers of at least one of three different LRRK2 gene mutations (G2019S, R1441C/G, or R1628P). Age and disease duration were found to predict baseline disease severity, while presence of at least one of these three LRRK2 mutations was a predictor of the rate of MDS-UPDRS Part I progression. The estimated progression rate in MDS-UPDRS Part I was 0.648 (95% confidence interval: 0.544, 0.739) points per year in noncarriers of a LRRK2 mutation and 0.259 (95% confidence interval: 0.217, 0.295) points per year in carriers of a LRRK2 mutation. This analysis demonstrates that the rate of progression based on MDS-UPDRS Part I is ~ 60% lower in carriers as compared with noncarriers of LRRK2 gene mutations.

Long term follow-up of visual acuity and incidence of subretinal neovascularization in Mactel Type 2 in 82 Eyes

ABSTRACT Purpose : To evaluate the long-term natural course of macular telangiectasia Type 2, correlation with visual acuity and the incidence of Choroidal Neovascularisation (CNV) in Indian eyes. Material and methods : A Retrospective analysis of Patients with MacTel Type 2 was done over a period of 12 years with all patients having a minimum of 3 years follow up. The demographic details and ocular characteristics including best-corrected visual acuity (BCVA), fundus photography, fluorescein angiography, and optical coherence tomography images were studied in both proliferative and non-proliferative MacTel. Mixed models were used to estimate progression rates and a Kaplan Meier estimation of BCVA was plotted. Results : Eighty-two eyes of 47 patients were studied over a period of mean duration of 4.5 years (range: 3 years-8.5 years). There was no difference in the demographic characteristics between the non-proliferative MacTel and proliferative MacTel groups. There were no significant risk factors observed for progression. However, patients with retinal greying had significant risk reduction for a BCVA decline. The mean logMAR BCVA decreased from 0.25 ± 0.25 at baseline to 0.46 ± 0.42 by 4 years. Twenty-eight percent of the patients maintained their vision 8 years from baseline and were unlikely to progress. The incidence of CNV was 10.6% and the mean duration for the development of CNV was 2.36 years from baseline. Seventy-Three percent (11 of 15) patients with CNV had a BCVA of <20/40. Conclusion : In patients of MacTel, the maximum vision loss occurred at the fourth year and then stabilized. The major cause of poor vision observed was CNV (active in 10.98% and scarred in 7.32%), foveal atrophy (10.98%) and central pigmented plaques (3.66%). The incidence of sight-threatening complication of CNV (10.6%) is likely to occur only in a minority of eyes.

Dynamics of detailed components of metabolic syndrome associated with the risk of cardiovascular disease and death

Few studies quantify a cascade of dynamic transitions on the detailed components of metabolic syndrome (MetS) and subsequent progressions to cardiovascular disease (CVD) and its death. A total of 47,495 subjects repeatedly attending a community-based integrated screening program in Taiwan were recruited. The refined MetS-related classification (RMRC) in relation to five criteria of MetS was defined as free of metabolic disorder (FMD, none of any criteria), mild metabolic disorder (MMD, 1–2 criteria) and MetS. A multistate Markov model was used for modelling such a multistate process. The estimated progression rate from FMD to MMD was 44.82% (95% CI 42.95–46.70%) whereas the regression rate was estimated as 29.11% (95% CI 27.77–30.45%). The progression rate from MMD to MetS was estimated as 6.15% (95% CI 5.89–6.42%). The estimated annual incidence rates of CVD increased with the severity of RMRC, being 1.62% (95% CI 1.46–1.79%) for FMD, 4.74% (95% CI 4.52–4.96%) for MMD, to 20.22% (95% CI 19.52–20.92%) for MetS. The estimated hazard rate of CVD death was 6.1 (95% CI 4.6–7.7) per thousand. Elucidating the dynamics of MetS-related transition and quantifying the incidence and prognosis of CVD provide a new insight into the design and the evaluation of intervention programs for CVD.

Longitudinal study of adherence to anticoagulation guidelines in patients with atrial fibrillation

Abstract Introduction Anticoagulation (AC) reduces the risk of stroke and systemic embolism (SSE) in patients with Atrial Fibrillation (AF). However, the association between changes in AF prevalence, risk factors for SSE, uptake of AC and incidence of SSE has not been documented specifically in these patients within a national population. Purpose Identifying antithrombotic prescribing and evaluating associations between changes in AF prevalence, SSE risk factors (CHA2DS2-VASC score) and uptake of AC. Evaluating relationships between changes in proportion of AF patients treated with AC and SSE rate at a population level. Developing a modelling tool which estimates rates of SSE (past and future) based on these factors, which can be used to drive improvements in health care. Method AF patients were identified in the population of Wales (SAIL databank) between 2012–2018. Temporal trends of AF, CHA2DS2-VASC scores, anti-thrombotic prescriptions and SSE events were evaluated. Multi-state Markov models were used to estimate SSE rates adjusted for AC and CHA2DS2-VASC scores. Simulation methods modelled SSE outcomes for the subsequent 7-years based on differing proportional population AC coverage. Results AF prevalence increased from 51,492 to 64,852 from 2012–18, with mean CHA2DS2-VASC score increasing from 3.0 to 3.9. AC prescription coverage increased (24,892 [48.3%] to 44,195 [68.1%]), whilst antiplatelet therapy alone or no antithrombotic therapy decreased (14,532 [28.0%] to 5,385 [8.3%] and 26,602 [52.0%] to 21,164 [33.0%] respectively). Hospitalisation rate for SSE in AF population decreased by over 20%, from 1,039 per 100,000 patients/quarter in 2012 to 809 per 100,000 patients/quarter in 2018. Markov modelling demonstrated a 39% lower SSE rate with AC compared to no AC over time, after adjustment for individual CHA2DS2-VASC (HR=0.61, 95% CI [0.58, 0.63]). Using the estimated progression rates, simulation models shown that an expected 3,574 SSE events per 100,000 per year could have been reduced to 2,956 (17% reduction rate) if AC adherence had been at the now recommended 90% rate from 2012. This model also predicts that improving AC coverage to 90% of patients over the next 7-years would reduce SSE rates by 12% per year (assuming no further increase in mean CHA2DS2-VASC score). Conclusion Despite the increase in both prevalence of AF and CHA2DS2-VASC between 2012–18, we observed a progressive decrease in SSE events along with increasing AC prescribing. Our study suggests not only that improved AC coverage is associated with better clinical outcomes, but also that the rate of therapeutic implementation is likely a crucial factor. Reducing transition time between evidence-based guideline publication and widespread clinical uptake of the recommendations appears to be an important opportunity to improve clinical outcomes at a population level and should inform healthcare policy development and implementation. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Funded by research grant

Disease Progression in Patients with Parkin-Related Parkinson's Disease in a Longitudinal Cohort.

There was a paucity of follow-up studies in the disease progression of early-onset PD patients with Parkin mutations (Parkin-EOPD). Here we conducted a longitudinal study to investigate the progression of motor and cognitive features of Parkin-EOPD patients. Genetic analysis was performed via target sequencing and multiplex ligation-dependent probe amplification. Thirty patients carrying homozygous or compound heterozygous Parkin mutations with at least 2 follow-up revisions were investigated as the Parkin-EOPD group. Fifty-two patients with at least 2 follow-up revisions, who did not have any known causative PD mutations, GBA or LRRK2 risk variants, a heterozygous Parkin mutation or 2 Parkin mutations without a segregation test, were defined as the genetically undefined EOPD (GU-EOPD) group. A linear mixed-effect model was implemented to evaluate longitudinal changes in motor symptoms and cognition. At baseline, the Parkin-EOPD group had a lower Unified Parkinson's Disease Rating Scale score (UPDRS-III) (off-medication) than the GU-EOPD group, without significant differences in cognition. A longitudinal study showed the estimated progression rate per year (standard error) of the UPDRS-III score (off-medication) was lower in the Parkin-EOPD group (0.203 [0.3162] points per year) than in the GU-EOPD group (1.056 [0.3001] points per year). The difference in the UPDRS-III score rate between the 2 groups was 0.853 (0.4183) (P = 0.042). The Parkin-EOPD group showed better maintenance of spatial processing ability compared with the GU-EOPD group (P = 0.027). Parkin-EOPD patients showed a slower deterioration of motor symptoms and a better spatial processing ability than GU-EOPD patients, which suggests that subtyping according to genetic features can help predict PD progression. © 2020 International Parkinson and Movement Disorder Society.

Retinal oedema in central retinal artery occlusion develops as a function of time

Time is the key criterion in the management of non-arteritic central retinal artery occlusion (NA-CRAO). However, the precise onset of vision loss is often difficult to determine. This study aimed to evaluate the temporal changes of retinal thickness in acute NA-CRAO and the potential of this parameter to be used as a surrogate marker to estimate the onset of retinal ischaemia. Optical coherence tomography was used to continuously assess retinal thickness and oedema progression rate in six porcine eyes. Additionally, a retrospective analysis of 12 patients with acute NA-CRAO was performed to determine association strength and progression rate between retinal thickness and onset of ischaemia. All Optical coherence tomography (OCT) scans (pigs and NA-CRAO patients) were performed within an ischaemic time frame of up to 9hr. Retinal oedema progression rate in pigs was 25.32µm/hr [CI 95%: 24.24-26.40µm/hr]. Retrospective analysis of the patients revealed a strong correlation between retinal oedema and duration of ischaemia (Spearman's rho=0.77, p=0.004) with an estimated progression rate of 10.02µm/hr [CI 95%: 3.30-16.74µm/hr]. Retinal thickness increases with oedema formation, and ischaemia onset is strongly correlated with this structural biomarker in both, pigs and NA-CRAO patients. Prospective clinical trials will have to determine the clinical feasibility of retinal thickness measurements as a biomarker to support clinical management of NA-CRAO.

Predictors of Progression in Patients With Stage B Aortic Regurgitation

BackgroundThe natural history of stage B aortic regurgitation (AR) is unknown. ObjectivesThis study sought to examine determinants, rate, and consequences of progression of AR. MethodsConsecutive patients with ≤moderate chronic AR quantified by effective regurgitant orifice area (EROA) and regurgitant volume (RVol) from 2004 to 2017 who had ≥1 subsequent echocardiogram with quantitation were included. ResultsOf 1,077 patients (66 ± 15 years of age), baseline trivial/mild AR was noted in 196 (18%), mild-to-moderate AR in 465 (43%), and moderate AR in 416 (39%); 10-year incidence of progression to ≥moderate-severe AR (stage C/D; progressors) was 12%, 30%, and 53%, respectively. At 4.1-year follow-up (interquartile range: 2.1 to 7.2 years), there were 228 progressors (21%), whose annualized progression rates within 3 years before diagnosis of ≥moderate-severe AR were 4.2 mm2/year for EROA and 9.9 ml/year for RVol. Baseline AR severity and dimensions of sinotubular junction and annulus were associated with progression (all p ≤ 0.007); hypertension and systolic blood pressure were not. Progressors had faster chamber remodeling, functional class decline, and more aortic valve/aortic surgery. At medium-term follow-up, 242 patients (22%) died; poor survival was linked to age, comorbidities, functional class, resting heart rate, and left ventricular (LV) ejection fraction (p ≤ 0.003), not LV end-systolic dimension index. Survival after progression to stage C/D AR was associated with LV end-systolic dimension index (adjusted p = 0.02). ConclusionsProgression from stage B to stage C/D AR was observed in 21% patients. Repeat echocardiography for trivial/mild, mild-to-moderate, and moderate AR at every 5, 3, and 1 years, respectively, was reasonable. EROA, RVol, annulus, and sinotubular junction should be routinely measured to estimate progression rates and identify patients at high risk of progression, which was associated with adverse consequences.

Incidence and predictors of recurrent and other new diabetic foot ulcers: a retrospective cohort study.

To estimate progression rates, evaluate risk factors for progression, and study rate ratios for progression among people with a healed diabetic foot ulcer according to whether the healed ulcer was neuropathic, neuro-ischaemic or critically ischaemic. We conducted a retrospective cohort study in all individuals with a healed diabetic foot ulcer treated at the Steno Diabetes Centre Copenhagen foot clinic in the period 2010 to 2016. The outcome of interest was recurrent/other new diabetic foot ulcers. A total of 780 people had a healed diabetic foot ulcer in the study period (2010-2016). The participants were followed for 1249 person-years [median (Q1-Q3) 1.04 (0.38-2.46) person-years] in total. One-third (33.1%) developed a recurrent/other new diabetic foot ulcer per year. Male gender, people with Type 2 diabetes and smokers had a statistically significantly higher risk of progression to a recurrent/other new diabetic foot ulcer compared to participants without these risk factors. Participants with neuro-ischaemic or critically ischaemic diabetic foot ulcers had statistically significantly higher progression rates than participants with neuropathic diabetic foot ulcers. Focus should be on preventing future recurrent/other new diabetic foot ulcers especially in people with ischaemia.

The Natural History of Idiopathic Scoliosis During Growth: A Meta-Analysis.

The aim of the study was to provide a meta-analysis of current literature concerning the natural history of idiopathic scoliosis during growth. A comprehensive search of Medline, Embase, And Scopus databases was conducted up to November 2016. Eligible works were prospective or retrospective studies that enrolled patients with infantile idiopathic scoliosis, juvenile idiopathic scoliosis, or adolescent idiopathic scoliosis, followed up without any treatment from the time of detection. A meta-analysis for proportion was performed. The following studies were grouped per diagnosis: infantile idiopathic scoliosis, juvenile idiopathic scoliosis, and adolescent idiopathic scoliosis. Of the 1797 citations screened, we assessed 61 full-text articles and included 13 of these (2301 participants). Three studies included infantile idiopathic scoliosis patients (347 participants), five studies included a mixed population of juvenile idiopathic scoliosis and adolescent idiopathic scoliosis (1330 participants), and five studies included adolescent idiopathic scoliosis patients only (624 participants). The random pooled estimated progression rate was 49% (95% confidence interval = 1%-97%) for infantile idiopathic scoliosis, 49% in a mixed group of patients affected by juvenile idiopathic scoliosis or adolescent idiopathic scoliosis (95% confidence interval = 19%-79%), and 42% in adolescent idiopathic scoliosis (95% confidence interval = 11%-73%). During growth, idiopathic scoliosis tends to progress in a high percentage of cases. The progression rate varies according to the age at diagnosis, with infantile scoliosis being the most unpredictable. There are many confounders, such as age, Risser sign and baseline Cobb angles that were not consistent among studies, making the data very heterogeneous.

Assessing uncertainty in the burden of hepatitis C virus: Comparison of estimated disease burden and treatment costs in the UK.

SummaryHepatitis C virus (HCV) is a major and growing public health concern. We need to know the expected health burden and treatment cost, and understand uncertainty in those estimates, to inform policymaking and future research. Two models that have been important in informing treatment guidelines and assessments of HCV burden were compared by simulating cohorts of individuals with chronic HCV infection initially aged 20, 35 and 50 years. One model predicts that health losses (measured in quality‐adjusted life‐years [QALYs]) and treatment costs decrease with increasing initial age of the patients, whilst the other model predicts that below 40 years, costs increase and QALY losses change little with age, and above 40 years, they decline with increasing age. Average per‐patient costs differ between the models by up to 38%, depending on the patients' initial age. One model predicts double the total number, and triple the peak annual incidence, of liver transplants compared to the other model. One model predicts 55%‐314% more deaths than the other, depending on the patients' initial age. The main sources of difference between the models are estimated progression rates between disease states and rates of health service utilization associated with different disease states and, in particular, the age dependency of these parameters. We conclude that decision‐makers need to be aware that uncertainties in the health burden and economic cost of HCV disease have important consequences for predictions of future need for care and cost‐effectiveness of interventions to avert HCV transmission, and further quantification is required to inform decisions.

CORRELATION OF CLINICAL AND STRUCTURAL PROGRESSION WITH VISUAL ACUITY LOSS IN MACULAR TELANGIECTASIA TYPE 2: MacTel Project Report No. 6-The MacTel Research Group.

To evaluate progression of macular telangiectasia Type 2 lesions and their correlation with visual acuity. An international multicenter prospective study with annual examinations including best-corrected visual acuity (BCVA), fundus photography, fluorescein angiography, and optical coherence tomography images graded centrally. Mixed models were used to estimate progression rates, and a generalized linear model to compute the relative risk of BCVA loss, loss of ellipsoid zone (EZ) reflectivity, development of pigment plaques, or neovascularization. One thousand and fourteen eyes of 507 participants were followed for 4.2 ± 1.6 years. Best-corrected visual acuity decreased 1.07 ± 0.05 letters (mean ± SE) per year. Of all eyes, 15% lost ≥15 letters after 5 years. Of the eyes without EZ loss, 76% developed a noncentral loss. Of the eyes with noncentral loss, 45% progressed to central EZ loss. The rate of BCVA loss in eyes with noncentral EZ loss at baseline was similar to eyes without EZ loss. The rate of BCVA loss was significantly higher in eyes with central EZ loss at baseline (-1.40 ± 0.14 letters, P < 0.001). Ellipsoid zone loss is frequently found in macular telangiectasia Type 2 and is an important structural component reflecting visual function. Its presence in the fovea significantly correlates with worse visual prognosis.

Clinical Significance of Diminutive Colonic Polyps in Elderly Patients.

Background and Objectives:Colorectal cancer is the third leading cause of cancer-related death. Excision of premalignant polyps has a significant impact on reducing colorectal cancer mortality and morbidity. Colonoscopy is considered to be the gold standard for the diagnosis and affords an opportunity for treatment of colonic polyps. In recent years, serious debates have taken place because of the biological characteristics of diminutive polyps (DPs), polypectomy complications, and serious costs. There has not yet been a consensus on the management of DPs. The objectives of this study were to demonstrate the real clinical importance of DPs smaller than 5 mm in diameter, which are frequently seen in geriatric patients by new endoscopic techniques, and to help in determining screening and surveillance programs.Methods:The patients who underwent colonoscopy and were found to have a diminutive colorectal polyp (<5 mm from September 1, 2016 through September 1, 2017), were classified into 3 groups according to the imaging method used: flexible spectral imaging color enhancement (FICE), narrow band imaging (NBI), or I-SCAN. In all groups, demographic data were compared according to Paris classification (morphologic) and Kudo classification (correlation between the prediction of endoscopic diagnosis and final pathological examination) in terms of sensitivity, specificity, and negative and positive predictive values.Results:Two hundred sixty-seven patients were included in the study: 97 in the NBI group, 83 in the FICE group, and 87 in the I-SCAN group. There were no statistically significant differences between NBI, FICE, and I-SCAN in differentiating neoplastic and nonneoplastic polyps, according to the Kruskal-Wallis test (P = .809).Conclusions:The estimated progression rates of DPs to advanced adenomas or colorectal cancer (CRC) are very low. Missing these polyps or not excising them may lead to failure to diagnose some cancers. There is a need for further comprehensive studies of removing all polyps to determine whether non–high-risk lesions require further pathologic examination and to re-examine routine surveillance programs.