Impact of Differential Rates of Disease Progression in Amyloid-Positive Early Alzheimer's Disease: Findings from a Longitudinal Cohort Analysis.

BACKGROUND: There is limited literature regarding the impact of differential rates of disease progression on longitudinal outcomes in individuals with early Alzheimer's disease (AD) and confirmed brain amyloid pathology. OBJECTIVES: To describe the underlying characteristics and long-term outcomes associated with different rates of disease progression among amyloid-positive individuals with early symptomatic AD. DESIGN: Retrospective observational study. SETTING: Data from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) in the United States (06/2005-11/2021). PARTICIPANTS: Individuals with a clinical assessment of mild cognitive impairment or dementia and Clinical Dementia Rating® Dementia Staging Instrument Sum of Boxes (CDR-SB) score 0.5-9.0 (inclusive; first visit defined as the index date) and confirmed amyloid positivity. Participants were stratified into No Progression (change ≤0), Slower Progression (0< change <2.0 points), Median Progression (2.0-point change), and Faster Progression (change >2.0 points) cohorts based on the observed distribution of changes in CDR-SB score between the index and first subsequent visit. MEASUREMENTS: For each cohort, the functional and neuropsychiatric outcomes were described at index and each subsequent visit for up to five years, and least-square (LS) mean changes from baseline were estimated using linear mixed-effects models adjusting for baseline demographic and clinical characteristics. RESULTS: Among 1,263 participants included in the analysis, the mean±standard deviation (SD) age at index was 72.7±9.7 years and 55.3% were males. Demographic characteristics and comorbidity profiles at index were similar across cohorts. However, at index, the Faster Progression (N=279) cohort had higher CDR-SB and Functional Assessment Questionnaire (FAQ) scores compared with the No Progression (N=474), Slower Progression (N=297), and Median Progression (N=213) cohorts. Adjusting for baseline characteristics, at year 5 after index the FAQ score increased by 23.6 points for Faster Progression cohort and 10.4, 15.8, and 19.2 points for the No, Slower, and Median Progression cohorts, respectively. The corresponding increases in Neuropsychiatric Inventory Questionnaire (NPI-Q) scores were 6.7 points for the Faster Progression cohort, and by 1.3, 3.1, and 8.3 points, for the No, Slower, and Median Progression cohorts, respectively. CONCLUSIONS: Despite similar demographic and clinical profiles at baseline, amyloid-positive individuals with greater deterioration based on CDR-SB early in the AD trajectory continue to experience worse functional and behavioral outcomes over time than those with more gradual deterioration in this metric.

Potential Implications of Slowing Disease Progression in Amyloid-Positive Early Alzheimer's Disease: Estimates from Real-World Data.

BACKGROUND: Emerging therapies have shown promising results for slowing the progression of Alzheimer's disease (AD). However, the potential impact of these therapies on real-world outcomes remains to be explored. OBJECTIVE: To examine the impact of slowing AD progression on functional abilities and behavioral symptoms. DESIGN: Retrospective observational study. SETTING: Data from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) in the United States (06/2005-11/2021, primary analysis) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (09/2005-03/2022, sensitivity analysis) were used. PARTICIPANTS: Individuals with mild cognitive impairment (MCI) or mild dementia, Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score 0.5-9.0 (inclusive; first visit defined as the index date), and confirmed amyloid positivity were identified in NACC. In ADNI, individuals with at least one clinical center visit with a clinical assessment of MCI or mild dementia and confirmed amyloid positivity were identified. MEASUREMENTS: Hypothetical effects of slowing disease progression as assessed by CDR-SB on functional and behavioral outcomes including the Functional Activities Questionnaire (FAQ) score, Neuropsychiatric Inventory Questionnaire (NPI-Q) score, and the probability of complete dependence over five years were evaluated using multivariable regression among NACC participants, separately for the subgroups with MCI and mild dementia at baseline, respectively. For the ADNI sensitivity analysis, the hypothetical effects of slowing disease progression were evaluated for FAQ score using multivariable regression among the MCI participants only. RESULTS: Compared with natural disease progression, slowing progression by 20% over five years for NACC participants with MCI and mild dementia, respectively, would result in 1.7-point (10.8%) and 1.6-point (12.9%) less deterioration based on FAQ; 0.5-point (20.3%) and 0.5-point (19.3%) less deterioration based on NPI-Q; 4.7 percentage-point (22.2%) and 10.1 percentage-point (21.6%) lower probability of complete dependence. Among ADNI participants, delaying disease progression by 20% or 30% over 4 years would avert deterioration based on FAQ of 1.1 points (20.4%) and 1.6 points (29.6%), respectively, compared to natural disease progression. CONCLUSIONS: Slowing early AD progression could result in preservation of functional and behavioral attributes and functional autonomy for longer.

The Outcome of Multicystic Dysplastic Kidney Disease Patients at King Abdulaziz Medical City in Riyadh.

Background Multicystic dysplastic kidney (MCDK) is a type of kidney dysplasia consisting of many irregular, various-sized cysts divided by dysplastic renal tissue, which negatively impacts kidney function. MCDK is one of the most common renal congenital disorders seen in antenatal ultrasounds. The typical prognosis of MCDK is complete or partial involution that starts antenatally and continues postnatally. The aim of the study was to shed light on the overall outcome of patients with MCDK. Methods We retrospectively collected data on MCDK patients from 2016 until 2022 at King Abdulaziz Medical City, Ministry of National Guard Health Affairs in Saudi Arabia, Riyadh. The data included the recording of epidemiological data, radiological and laboratory reports, and the presence of urological or non-urologically associated anomalies. Results A total of 57 patients with MCDK were reviewed. Seven of them were excluded due to the diagnosis of bilateral MCDK, which was incompatible with life. Of the remaining 50 patients, the right kidney was affected in 52% of them. Most patients were diagnosed antenatally (98%). The mean duration of follow-up for the study was 48 months. Vesicoureteral reflux (VUR) was detected in 22% of the total sample. Overall, 90% of the patients underwent kidney involution. A small percentage had genitourinary anomalies (20%), while a larger percentage (48%) had extrarenal abnormalities. Conclusion Multicystic dysplastic kidney disease is relatively common in children. The prognosis is affected by the presence of genitourinary and non-genitourinary anomalies. Patients have an overall good prognosis with conservative management. Antenatal screening, diagnosis, and long-term nephrological follow-up are essential for the optimal management of patients.

Factors Associated With Emergency Department Visits or Readmission of Late Preterm Infants at the Neonatal Intensive Care Department, National Guard Health Affairs, Riyadh.

Background Infants who are born between 34 0/7 and 36 6/7 weeks of pregnancy as a result of maternal or fetal factors are defined as "late preterm infants". Compared to term infants, late preterm infants are more predisposed to pregnancy complications because they are less mature physiologically and metabolically. In addition, health practitioners still face difficulties in differentiating between term and late preterm infants due to similar general appearance. The aim of this study is to explore the epidemiology of readmission among late preterm infants at the National Guard Health Affairs. The objectives of the study were to calculate the rate of readmission among late preterm infants in the first month after discharge and to identify the associated risk factors for readmission. Methods A retrospective cross-sectional study was carried out at the neonatal intensive care unit (NICU at King Abdulaziz Medical City in Riyadh). We identified preterm infants born in 2018 and the risk factors for readmission within the first month of life. Data on risk factors were collected using the electronic medical file. Results A total of 249 late preterm infants with a mean gestational age of 36 weeks were included in the study. Of them, 64 infants (25.7%) suffered from at least a subsequent admission and stayed overnight in either the inpatient department or pediatric emergency room. Maternal diabetes was a significant risk factor for readmission; on the other hand, a positive maternal Rh factor was a protective factor against readmission. Among readmitted infants (n=64), 51 infants were admitted to the emergency room (79.69%), eight infants were readmitted to the pediatric ward (12.5%), and five infants were readmitted to both (7.8%). The most common cause for pediatric ER visits was gastrointestinal (GIT) problems (27%), followed by upper respiratory tract infection (URTI) (18%) and jaundice (14%). The most common cause for direct ward readmission was jaundice (n= 5; 62%). Conclusion Gastrointestinal (GIT) issues and upper respiratory tract infections (URTIs) were the leading causes of pediatric emergency room admissions. In contrast, jaundice, congenital diaphragmatic hernia (CDH), airway problems, and regurgitation were the most frequent causes of admission to the ward, with jaundice being the primary cause. Although studies suggest that the late preterm population is at a higher risk for long-term health issues, further research is necessary to investigate this topic thoroughly.

Increasing COVID-19 vaccination in the United States: projected impact on cases, hospitalizations, and deaths by age and racial group.

OBJECTIVES: Minority populations in the United States face a disproportionate burden of illness from COVID-19 infection and have lower vaccination rates compared with other groups. This study estimated the equity implications of increased COVID-19 vaccination in the United States, with a focus on the number of cases, hospitalizations, and deaths avoided. STUDY DESIGN: This was an observational real-world modeling study. METHODS: Data from the Centers for Disease Control and Prevention (CDC) were used to identify the remaining unvaccinated US population by county, age, and race as of October 22, 2021. The number of COVID-19 cases, hospitalizations, and deaths avoided were calculated based on case incidence and death data from the CDC, along with data on race- and age-specific hospitalization multipliers, under a scenario in which half of the remaining unvaccinated population per county, race, and age group obtained a full vaccine regimen. RESULTS: Vaccinating half of the remaining unvaccinated population in each age and race subgroup within counties would result in an estimated 22.09 million COVID-19 cases avoided, 1.38 million hospitalizations avoided, and 150,000 deaths avoided over 12 months. Some minority groups, particularly Black and Hispanic/Latino populations, were projected to experience substantial benefits from increased vaccination rates as they face both lower vaccination rates and worse outcomes if infected with COVID-19. CONCLUSIONS: Increasing COVID-19 vaccination in the United States not only benefits the population as a whole but also serves as a potentially useful lever to reduce the disproportionate burden of COVID-19 illness among minority populations.