To re-evaluate the population-based incidence of idiopathic intracranial hypertension (IIH) and to determine if it mirrors the rise in obesity.
Retrospective, population-based cohort.
All residents ...of Olmsted County, Minnesota, diagnosed with IIH between January 1, 1990, and December 31, 2014.
All cases of IIH were identified using the Rochester Epidemiology Project, which is a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota, residents. All medical records were reviewed to confirm a diagnosis of IIH. The incidence rates of IIH were compared against the incidence of obesity in Minnesota over the same period.
Incidence of IIH, lumbar puncture opening pressures, and body mass index.
There were 63 new cases of IIH, yielding an overall age- and gender-adjusted annual incidence of 1.8 per 100 000 (95% confidence interval, 1.3-2.2) between 1990 and 2014. It increased from 1.0 per 100 000 (1990-2001) to 2.4 per 100 000 (2002-2014; P = 0.007). The incidence of IIH was 3.3 per 100 000 in women and 0.3 per 100 000 in men (P ≤ 0.001). In obese women 15 to 44 years of age, the incidence was 22.0 per 100 000 compared with 6.8 per 100 000 among all women in the same age group. A strong correlation was observed between IIH incidence rates and obesity rates in Minnesota (R
= 0.70, P = 0.008).
The incidence of IIH has increased since 1990, which is highly correlated with the rise in obesity during the same period.
Plasma phosphorylated tau 181 (P-tau181) and 217 (P-tau217) are indicators of both amyloid and tau pathology in clinical settings, but their performance in heterogeneous community-based populations ...is unclear. We examined P-tau181 and P-tau217 (n = 1,329, aged 30-98 years), in the population-based Mayo Clinic Study of Aging. Continuous, unadjusted plasma P-tau181 and P-tau217 predicted abnormal amyloid positron-emission tomography (PET) (area under the receiver operating characteristic curve (AUROC) = 0.81-0.86) and tau PET entorhinal cortex (AUROC > 0.80), but was less predictive of a tau PET temporal region of interest (AUROC < 0.70). Multiple comorbidities were associated with higher plasma P-tau181 and P-tau217 levels; the difference between participants with and without chronic kidney disease (CKD) was similar to the difference between participants with and without elevated brain amyloid. The exclusion of participants with CKD and other comorbidities affected the establishment of a normal reference range and cutpoints. Understanding the effect of comorbidities on P-tau181 and P-tau217 levels is important for their future interpretation in the context of clinical screening, diagnosis or prognosis at the population level.
The literature on the prevalence and demographics of congenital nasolacrimal duct obstruction (CNLDO) is 30-70 years old and largely comprises small sample sizes. This study provides epidemiological ...findings of this common disorder from the largest cohort reported to date.
The medical records of all children (<5 years of age) residing in Olmsted County, Minnesota, when diagnosed with CNLDO from 1 January 1995 through 31 December 2004, were reviewed.
Of 17 713 newborns born during the 10-year study period, 1998 were diagnosed with CNLDO, yielding a birth prevalence of one in nine live births. The diagnosis was made in approximately 90% by a primary care physician, at a median age of 5 weeks, with no gender predilection. Compared with the reference population, CNLDO was associated with premature birth (p=0.005) and was more prevalent among Caucasians (p<0.001). Two-thirds of patients initially presented with discharge alone, 18% with tearing alone and 15% with both discharge and tearing.
In this large population-based cohort, CNLDO occurred in one in nine live births with no gender predilection. Prematurity and Caucasian race were associated with the development of CNLDO. Mucopurulent discharge was a much more common feature than tearing at initial presentation.
IMPORTANCE: Cerebrospinal fluid phosphorylated tau (p-tau) 181, p-tau217, and p-tau231 are associated with neuropathological outcomes, but a comparison of these p-tau isoforms in blood samples is ...needed. OBJECTIVE: To conduct a head-to-head comparison of plasma p-tau181 and p-tau231 measured on the single-molecule array (Simoa) platform and p-tau181 and p-tau217 measured on the Meso Scale Discovery (MSD) platform on amyloid and tau positron emission tomography (PET) measures, neurodegeneration, vascular pathology, and cognitive outcomes. DESIGN, SETTING, AND PARTICIPANTS: This study included data from the Mayo Clinic Study on Aging collected from March 1, 2015, to September 30, 2017, and analyzed between December 15, 2020, and May 17, 2021. Associations between the 4 plasma p-tau measures and dichotomous amyloid PET, metaregion of interest tau PET, and entorhinal cortex tau PET were analyzed using logistic regression models; the predictive accuracy was summarized using area under the receiver operating characteristic curve (AUROC) statistic. Of 1329 participants without dementia and with p-tau181 and p-tau217 on MSD, 200 participants with plasma p-tau181 and p-tau231 on Simoa and magnetic resonance imaging and amyloid and tau PET data at the same study visit were eligible. MAIN OUTCOMES AND MEASURES: Primary outcomes included amyloid (greater than 1.48 standardized uptake value ratio) and tau PET, white matter hyperintensities, white matter microstructural integrity (fractional anisotropy genu of corpus callosum and hippocampal cingulum bundle), and cognition. RESULTS: Of 200 included participants, 101 (50.5%) were male, and the median (interquartile range IQR) age was 79.5 (71.1-84.1) years. A total of 177 were cognitively unimpaired (CU) and 23 had mild cognitive impairment. Compared with amyloid-negative CU participants, among amyloid-positive CU participants, the median (IQR) Simoa p-tau181 measure was 49% higher (2.58 2.00-3.72 vs 1.73 1.45-2.13 pg/mL), MSD p-tau181 measure was 53% higher (1.22 0.91-1.56 vs 0.80 0.66-0.97 pg/mL), MSD p-tau217 measure was 77% higher (0.23 0.17-0.34 vs 0.13 0.09-0.18 pg/mL), and Simoa p-tau231 measure was 49% higher (20.21 15.60-25.41 vs 14.27 11.27-18.10 pg/mL). There were no differences between the p-tau species for amyloid PET and tau PET metaregions of interest. However, among CU participants, both MSD p-tau181 and MSD p-tau217 more accurately predicted abnormal entorhinal cortex tau PET than Simoa p-tau181 (MSD p-tau181: AUROC, 0.80 vs 0.70; P = .046; MSD p-tau217: AUROC, 0.81 vs 0.70; P = .04). MSD p-tau181 and p-tau217 and Simoa p-tau181, but not p-tau231, were associated with greater white matter hyperintensity volume and lower white matter microstructural integrity. CONCLUSIONS AND RELEVANCE: In this largely presymptomatic population, these results suggest subtle differences across plasma p-tau species and platforms for the prediction of amyloid and tau PET and magnetic resonance imaging measures of cerebrovascular and Alzheimer-related pathology.
Frailty and disability from arthritis are closely intertwined and little is known about the impact of frailty on total hip arthroplasty (THA) outcomes. We hypothesized that higher preoperative ...frailty is associated with more adverse events following THA.
All patients (≥50 years) undergoing unilateral primary or revision THA at a single institution from 2005 through 2016 were included. We analyzed the association of frailty (measured by a frailty deficit index) with postoperative outcomes in hospital, within 90 days, and within 1 year using multivariable logistic and Cox regression, adjusting for age.
Among 8640 patients undergoing THA (6502 primary and 2138 revisions; median age 68 years), 22.7%, 32.9%, and 44.4% were classified as frail, vulnerable, and nonfrail, respectively. Frail patients tended to be female, older, sicker (American Society of Anesthesiologists ≥3), and received general anesthesia more frequently. Relative to nonfrail patients, frail patients had significantly increased odds of wound complications/hematoma (odds ratio 2.01) and reoperation (odds ratio 2.74) while in hospital, and increased risks for mortality (1-year hazards ratio HR 5.65), infection (1-year HR 3.63), dislocation (1-year HR 2.10), wound complications/hematoma (1-year HR 2.61), and reoperation (1-year HR 2.22) within 90 days and 1 year. Frailty was also associated with >5.5-fold increased mortality risk 1 year following THA. No significant associations with aseptic loosening, periprosthetic fracture, or heterotopic ossification were observed.
A higher preoperative frailty index is associated with increased mortality and perioperative complications following primary and revision THA. The proposed frailty deficit index provides clinically important information for healthcare providers to use when counseling patients prior to decision for surgery.
IMPORTANCE: Although the overall rate of spontaneous resolution in congenital nasolacrimal duct obstruction (CNLDO) and efficacy of probing have been documented in the literature, the optimal timing ...of intervention has not been established. OBJECTIVE: To report new findings regarding spontaneous resolution in a large cohort of children with CNLDO. DESIGN, SETTING, AND PARTICIPANTS: The medical records of 1998 consecutive infants diagnosed with CNLDO from January 1, 1995, through December 31, 2004, while residing in Olmsted County, Minnesota, were retrospectively reviewed. Data were analyzed between January 1, 2015, and January 2017. MAIN OUTCOMES AND MEASURES: Rate of spontaneous resolution over time and by sex. RESULTS: The cohort, diagnosed at a median age of 1.2 months (interquartile range, 0.4-3.6), was 48% girls (n = 959) and 89% white (n = 1626; 173 were unreported). Among the 1998 cases, 1669 (83.5%) spontaneously resolved, 289 (14.5%) underwent treatment, and the remaining 40 (2.0%) were lost to follow-up. Of the 1958 infants followed up, CNLDO in 925 (47.3%) spontaneously resolved by age 3 months, in 1300 (66.4%) by 6 months, in 1472 (75.7%) by 9 months, and in 1516 (78.4%) by 12 months. The rate of resolution was 35% faster (95% CI, 23%-47%; P < .001) at less than 1 month vs 3 months, 43% faster (95% CI, 27%-64%; P < .001) at 3 months vs 6 months, 39% faster (95% CI, 16%-64%; P < .001) at 6 months vs 9 months, and 1% slower at 9 months vs 12 months (hazard ratio, 0.99; 95% CI, 0.80-1.22; P = .78). Congenital nasolacrimal duct obstruction resolved in boys 0.5 months (95% CI, 0.2-0.8; P < .001) faster than girls (median, 2.9 vs 3.4 months), and unilateral obstructions resolved 0.2 months (95% CI, 0.1-0.4; P = .002) faster than bilateral (median, 3.1 vs 3.3 months) ones. Children probed at 15 months or older had decreased odds of resolution after probing (odds ratio, 0.11; 95% CI, 0.01-0.89; P = .04) compared with children probed at age 12 to 14 months. CONCLUSIONS AND RELEVANCE: Based on this large cohort of children with CNLDO, probing between age 9 and 15 months may be reasonable given that the rate of spontaneous resolution plateaued after 9 months and initial probing success declined after 15 months. This time frame supports both an earlier and narrower range of ages for intervention compared with the current practice of probing after age 1 year.
Incisional hernias represent an acquired defect from failed healing of an abdominal facial incision and are therefore distinct from primary hernias. While literature regarding incisional hernia ...incidence, risk factors, and treatment are abundant, no study has examined national health disparities specific to incisional hernia repair. The objective of this study was to analyze national health disparities unique to surgical incisional hernia repair procedures.
Patient data queried from the Healthcare Cost and Utilization Project National Inpatient Sample from 2012 to 2014 using International Classification of Diseases 9th revision procedure codes for incisional hernia repair were used to generate univariate and multivariate models including demographics, socioeconomic factors, admission status, and hospital characteristics. Primary outcomes were nonelective admission status, in-hospital mortality, surgical complications, and extended duration of stay.
We estimated that 89,258 incisional hernia repair procedures occurred annually from 2012 to 2014, incurring $6.3 billion in hospital charges. By multivariate analysis, multiple risk factors contribute to significantly increased odds of nonelective repair. These include age over 65, female sex, non-White race, nonprivate insurance, obesity, and increased Charlson comorbidity index. Nonelective incisional hernia repair was strongly correlated with worse outcomes including in-hospital mortality (odds ratio 95% confidence interval 3.01 2.51, 3.61), postoperative complications (odds ratio 1.2 1.14, 1.25), and extended duration of stay (odds ratio 2.96 2.81, 3.12). After controlling for admission status, other disparities persisted including extended duration of stay for Black individuals (odds ratio 1.21 (1.12, 1.31).
Providers should be aware of these significant health disparities in incisional hernia repair status and outcomes especially for elderly, non-White, nonprivate insurance, and obese/comorbid patients. Management strategies that increase access to elective repair and that prevent incisional hernia should be expanded to address these disparities.
X-linked hypophosphatemia (XLH) is caused by a loss-of-function mutation in the phosphate regulating gene with homology to endopeptidase located on the X chromosome (PHEX). Loss of functional PHEX ...results in elevated fibroblast growth factor 23 (FGF23), impaired phosphate reabsorption, and inhibited skeletal mineralization. Sclerostin, a protein produced primarily by osteocytes, suppresses bone formation by antagonizing canonical Wnt-signaling and is reported to be elevated in XLH patients. Our previous study reported that a monoclonal antibody to sclerostin (Scl-Ab) decreases FGF23 and increases phosphate and bone mass in growing Hyp mice (XLH murine model). In the current study, we investigated the efficacy of Scl-Ab in treating XLH pathophysiology in adult Hyp mice that are past the period of rapid skeletal growth (12 and 20-weeks old). We hypothesized that Scl-Ab would not only increase bone formation, bone strength and bone mass, but would also normalize phosphate regulating hormones, FGF23, parathyroid hormone (PTH), and vitamin 1,25(OH)2D. Scl-Ab treatment increased cortical area, trabecular bone volume fraction, trabecular bone formation rate, and the bending moment in both sexes of both age groups. Scl-Ab treatment suppressed circulating levels of intact FGF23 and c-term FGF23 in treated male and female wild-type and Hyp mice of both age groups and improved both vitamin 1,25(OH)2D and PTH. Scl-Ab treated Hyp mice also showed evidence of increased renal expression of the sodium-phosphate co-transporter, NPT2a, specifically in the female Hyp mice. Our study suggests that Scl-Ab treatment can improve several skeletal and metabolic pathologies associated with XLH, further establishes the role of sclerostin in the regulation of FGF23 and provides evidence that Scl-Ab can improve phosphate regulation by targeting the bone-renal axis.
•Sclerostin antibody decreases fibroblast growth factor-23, increases vitamin 1,25(OH)2D, and decreases parathyroid hormone in adult Hyp mice.•Sclerostin antibody treatment increases bone mass, bone formation rate, and bone strength in adult Hyp mice.•Sclerostin antibody treatment increases NPT2a protein expression, particularly in female Hyp mice.
Cerebral amyloid angiopathy (CAA) often coexists with Alzheimer’s disease (AD).
APOE4
is a strong genetic risk factor for both AD and CAA. Sex-dependent differences have been shown in AD as well as ...in cerebrovascular diseases. Therefore, we examined the effects of
APOE4
, sex, and pathological components on CAA in AD subjects. A total of 428 autopsied brain samples from pathologically confirmed AD cases were analyzed. CAA severity was histologically scored in inferior parietal, middle frontal, motor, superior temporal and visual cortexes. In addition, subgroups with severe CAA (
n
= 60) or without CAA (
n
= 39) were subjected to biochemical analysis of amyloid-β (Aβ) and apolipoprotein E (apoE) by ELISA in the temporal cortex. After adjusting for age, Braak neurofibrillary tangle stage and Thal amyloid phase, we found that overall CAA scores were higher in males than females. Furthermore, carrying one or more
APOE4
alleles was associated with higher overall CAA scores. Biochemical analysis revealed that the levels of detergent-soluble and detergent-insoluble Aβ40, and insoluble apoE were significantly elevated in individuals with severe CAA or
APOE4
. The ratio of Aβ40/Aβ42 in insoluble fractions was also increased in the presence of CAA or
APOE4
, although it was negatively associated with male sex. Levels of insoluble Aβ40 were positively associated with those of insoluble apoE, which were strongly influenced by CAA status. Pertaining to insoluble Aβ42, the levels of apoE correlated regardless of CAA status. Our results indicate that sex and
APOE
genotypes differentially influence the presence and severity of CAA in AD, likely by affecting interaction and aggregation of Aβ40 and apoE.
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