Progressive Supranuclear palsy (PSP) disease progression, management, and healthcare resource utilization: a retrospective observational study in the US and Canada.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative brain disease with rapid progression and currently limited treatment options. A comprehensive understanding of disease progression, management, and healthcare resource utilization is limited, and further research is challenging due to the small population of patients. To address these challenges in conducting PSP research, individuals with PSP were recruited using a multichannel approach tailored specifically to the PSP community. We performed a retrospective observational study using data abstracted from participant medical records collected from multiple patient care centers. RESULTS: Seventy-two individuals with PSP were eligible for inclusion. On average, 144 medical documents per participant were collected from an average of 2.9 healthcare centers per participant, with a mean study period of 7.9 years. Among participants with a date of symptom onset documented in the medical records, the median time for the onset of the first fall was 2.0 years (IQR 3.2) before diagnosis, the median onset of unsteady gait or gait impairment was 1.2 years (IQR 1.8) before diagnosis, and the median onset of mobility problems was 0.8 years (IQR 1.8) before diagnosis. The most widely utilized healthcare resources, with at least 85% of participants using each of these resources at some point during the disease course, were medications (100%), imaging (99%), assistive devices (90%), supportive care (86%), and surgeries and procedures (85%). CONCLUSIONS: This retrospective study adds to the current understanding of PSP symptoms, comorbidities, and healthcare resource utilization (HRU) across the disease journey. By involving individuals with PSP and their caregivers or legally authorized representatives in the research process, this study was unique in its approach to participant recruitment and enabled individuals to participate in research without the need for travel. We collected medical documents from multiple healthcare centers, allowing for broad data collection covering the entire disease journey. This approach to the collection of real-world data may be used to generate valuable insights into many aspects of disease progression and management in PSP and many other rare diseases.

Receipt of Electroconvulsive Therapy and Subsequent Development of Amyotrophic Lateral Sclerosis: A Cohort Study.

We investigated the potential relationship between receipt of electroconvulsive therapy (ECT) and development of amyotrophic lateral sclerosis (ALS). We conducted a cohort study using a sample of more than one million beneficiaries enrolled in the U.S. Medicare health insurance program from 1997 to 2017. Using time-varying proportional hazard modeling, we compared ALS occurrence among patients diagnosed with psychiatric conditions who received ECT to ALS occurrence among patients diagnosed with psychiatric conditions but who did not receive ECT. We observed moderately increased, but imprecise, hazard ratios (HR) for ALS following ECT (HR = 1.39, 95% confidence interval [CI]: 0.69-2.80). A statistically significant increase in the HR of ALS was observed among those who received more than 10 ECT treatments (>10 treatments, HR = 2.24, 95% CI: 1.00-5.01), compared to those receiving no ECT, with an even stronger association observed among subjects older than 65 years (HR = 3.03, 95% CI: 1.13-8.10). No monotonic exposure-response relationship was detected in categorical analyses. Our results provide weak support for the hypothesis that receipt of ECT increases the risk of developing ALS. Additional studies in larger populations, or in populations where ECT is more common, will be needed to refute or confirm an association between receipt of ECT and subsequent development of ALS. Bioelectromagnetics. 43:81-89, 2022. © 2021 Bioelectromagnetics Society.

Teratogen update: Topical use and third-generation retinoids.

The first pharmaceutical retinoids approved by the U.S. Food and Drug Administration were given black-box warnings against their use in pregnancy due to potential teratogenic effects. These first- and second-generation retinoids were initially formulated for oral dosing and are structurally very similar to vitamin A, which has beneficial effects on skin as well as plays a vital role in driving healthy embryogenesis. Some of these early retinoids have since been reformulated for topical application, which has resulted in their diminished potential for systemic exposures. Additionally, rational drug design has been applied to create today's third-generation retinoids (adapalene, tazarotene, and bexarotene). These compounds include aromatic rings within their molecular cores to provide structural rigidity that contrasts with the flexible aliphatic backbone of vitamin A and the earlier generations of retinoids, and thus limits their off-target activity. As a result of these design features, the teratogenic potential in animals of the third-generation retinoids and those reformulated for topical use is generally less than seen with oral administration of earlier generations of retinoids. The available, but limited, epidemiologic data further show little-to-no teratogenic potential associated with real-life use of these compounds in humans. Given the paucity of epidemiologic data available at this time, however, it is recommended that the use of topical retinoids during pregnancy be avoided. However, in circumstances when inadvertent exposure in pregnancy may occur, the available data provide some reassurance that adverse pregnancy outcomes are unlikely.

How Well Do U.S. Hispanics Adhere to the Dietary Guidelines for Americans? Results from the Hispanic Community Health Study/Study of Latinos.

Purpose: To examine alignment between 2010 Dietary Guidelines for Americans (DGA) and dietary choices of individuals in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) between 2008 and 2011. Methods: Data are from 15,633 adults 18-74 years from the population-based cohort in HCHS/SOL. The Healthy Eating Index (HEI) 2010 was used to measure diet quality. Means and standard errors (SEs) for the HEI total and each of the 12 component scores were calculated overall and by Hispanic/Latino heritage, sex, age group, and measures of acculturation. Linear regression was used to examine correlates of the HEI 2010 total score. All analyses accounted for complex survey design. Results: The overall HEI mean of 63.8 (SE: 0.4) varied across groups from a high (healthier diet) of 71 (SE: 0.9) among Mexicans to a low of 56 (SE: 0.1) among Puerto Ricans. The proportion with a maximum score for the HEI components varied across heritage groups; >25% of adults adhered to recommendations for total proteins, and seafood and plant proteins, whole fruits, and greens and beans, with the exception of Cubans and Puerto Ricans, who had lower adherence scores for the latter two. The components with the lowest adherence were sodium (<2%) and fatty acids (overall 7.4%) among all heritage groups. Characteristics associated with better adherence included sociodemographic variables, Spanish language preference, weight status, medical conditions, and lifestyle behaviors. Conclusions: Individuals with Mexican, Dominican, and Central American heritage had better overall dietary quality compared to other groups. However, all can improve their eating habits to align more with the DGAs by reducing sodium consumption and improving fatty acid ratios.

Survival of infants with spina bifida and the role of maternal prepregnancy body mass index.

OBJECTIVE: To investigate first-year survival of infants born with spina bifida, and examine the association of maternal prepregnancy body mass index (BMI) with infant mortality. METHODS: This is a retrospective cohort study of 1,533 liveborn infants with nonsyndromic spina bifida with estimated dates of delivery from 1998 to 2011 whose mothers were eligible for the National Birth Defects Prevention Study (NBDPS). NBDPS data were linked to death records to conduct survival analyses. Kaplan-Meier survival functions estimated mortality risk over the first year of life. Cox proportional hazards models estimated hazard ratios (HRs) for maternal prepregnancy BMI categorized as underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), and obese (≥30). RESULTS: Infant mortality risk among infants with spina bifida was (4.4% [3.52, 5.60%]). Infants with multiple co-occurring defects, very preterm delivery, multiple gestation, high-level spina bifida lesions, or non-Hispanic Black mothers had an elevated risk of infant mortality. Maternal prepregnancy underweight and obesity were associated with higher infant mortality (15.7% [7.20, 32.30%] and 5.82% [3.60, 9.35%], respectively). Adjusted HR estimates showed underweight and obese mothers had greater hazard of infant mortality compared to normal weight mothers (HR: 4.5 [1.08, 16.72] and 2.6 [1.36, 8.02], respectively). CONCLUSION: The overall risk of infant mortality for infants born with spina bifida was lower than most previously reported estimates. Infants born with spina bifida to mothers who were underweight or obese prepregnancy were at higher risk of infant mortality. This study provides additional evidence of the importance of healthy maternal weight prior to pregnancy.

Impact of chloroform exposures on reproductive and developmental outcomes: A systematic review of the scientific literature.

AIMS: We assessed the animal and epidemiological data to determine if chloroform exposure causes developmental and/or reproductive toxicity. RESULTS AND DISCUSSION: Initial scoping identified developmental toxicity as the primary area of concern. At levels producing maternal toxicity in rats and mice, chloroform caused decrements in fetal weights and associated delays in ossification. In a single mouse inhalation study, exposure to a high concentration of chloroform was associated with small fetuses and increased cleft palate. However, oral exposure of mice to chloroform at a dose 4 times higher was negative for cleft palate; multiple inhalation studies in rats were also negative. Epidemiologic data on low birth weight and small for gestational age were generally equivocal, preventing conclusions from being drawn for humans. The animal data also show evidence of very early (peri-implantation) total litter losses at very high exposure levels. This effect is likely maternally mediated rather than a direct effect on the offspring. Finally, the epidemiologic data indicate a possible association of higher chloroform exposure with lower risk of preterm birth (<37 weeks gestation). CONCLUSIONS: The available animal data suggest that exposures lower than those causing maternal toxicity should be without developmental effects in the offspring. Also, most studies in humans rely on group-level geographic exposure data, providing only weak epidemiologic evidence for an association with development outcomes and fail to establish a causal role for chloroform in the induction of adverse developmental outcomes at environmentally relevant concentrations.

Sociodemographic Factors and Survival of Infants With Congenital Heart Defects.

OBJECTIVES: To examine the first-year survival of infants with congenital heart defects (CHDs) and investigate the potential role of socioeconomic and demographic factors on survival. METHODS: Subjects included 15 533 infants with CHDs born between 2004 and 2013 ascertained by the NC Birth Defects Monitoring Program. We classified CHDs into the following 3 groups: critical univentricular (n = 575), critical biventricular (n = 1494), and noncritical biventricular (n = 13 345). We determined vital status and age at death through linkage to state vital records and used geocoded maternal residence at birth to obtain census information for study subjects. We calculated Kaplan-Meier survival estimates by maternal and infant characteristics and derived hazard ratios from Cox proportional hazard models for selected exposures. RESULTS: Among all infants with CHDs, there were 1289 deaths (8.3%) in the first year. Among infants with univentricular defects, 61.6% (95% confidence interval [CI]: 57.7%-65.7%) survived. Survival among infants with univentricular defects was considerably better for those whose fathers were ≥35 years old (71.6%; 95% CI: 63.8%-80.3%) compared with those whose fathers were younger (59.7%; 95% CI: 54.6%-65.2%). Factors associated with survival among infants with any biventricular defect included maternal education, race and/or ethnicity, marital status, and delivery at a heart center. The hazard of infant mortality was greatest among non-Hispanic African American mothers. CONCLUSIONS: Survival among infants with critical univentricular CHDs was less variable across sociodemographic categories compared with survival among infants with biventricular CHDs. Sociodemographic differences in survival among infants with less severe CHDs reinforces the importance of ensuring culturally effective pediatric care for at-risk infants and their families.

Antioxidant Consumption is Associated with Decreased Odds of Congenital Limb Deficiencies.

BACKGROUND: Approximately 1 in 2000 infants is born with a limb deficiency in the US. Research has shown that women's periconceptional diet and use of vitamin supplements can affect risk of birth defects. We investigated whether maternal consumption of nutritional antioxidants was associated with occurrence of transverse limb deficiency (TLD) and longitudinal limb deficiencies (LLD). METHODS: We analysed case-control data from mothers and their singleton infants with TLD (n = 566), LLD (n = 339), or no malformation (controls; n = 9384) in the National Birth Defects Prevention Study (1997-2009). Using a modified food frequency, we estimated usual pre-pregnancy antioxidant consumption by total fruit and vegetable consumption (in grams) grouped into tertiles, and cumulative antioxidant score (ranging from 1 to 10) based on consumption of three antioxidants: beta-carotene, lycopene, and lutein. We estimated odds ratios (OR) adjusted for maternal age, race/ethnicity, education, smoking, alcohol use, body mass index, and total energy. RESULTS: Compared to women in the lowest tertile of fruit and vegetable consumption, women in the highest tertile were less likely to have infants with TLD (OR 0.74, 95% CI 0.57, 0.96) or LLD (OR 0.82, 95% CI 0.59, 1.13). Compared to the lowest antioxidant consumption score of 1, those with the highest score of 10 had ORs of 0.68 (95% CI 0.48, 0.95) for TLD and 0.77 (95% CI 0.50, 1.17) for LLD. CONCLUSIONS: Dietary intake of antioxidants was associated with reduced odds of limb deficiencies. These findings add further evidence for women's periconceptional diet reducing occurrence of some birth defects.

Cutaneous malignant melanoma among white Hispanics and non-Hispanics in the United States.

AIM: To explore whether disparities exist in melanoma incidence and prognosis between White Hispanics and White non-Hispanics. METHODS: Analyses were based on 42,770 patients with malignant melanoma in the United States, 2004 through 2006. RESULTS: Hispanics were significantly less likely to be diagnosed with superficial spreading melanoma or Hutchinson's melanotic freckle, but significantly more likely to be diagnosed with nodular melanoma or acral lentiginous melanoma. Hispanics were also significantly less likely to have multiple primary cancers and less likely to receive surgical treatment. Among those diagnosed during the study period, 12.4% (n = 142) of Hispanic patients and 8.5% (n = 3,235) of non-Hispanic patients died sometime during these years. Approximately 7.3% of Hispanic patients and 4.8% of non-Hispanic patients died specifically from melanoma. Later stage at diagnosis was the primary explanation for the difference in death from melanoma between Hispanic and non-Hispanic Whites. CONCLUSIONS: Hispanic melanoma patients experience significantly poorer prognostic findings at diagnosis. The disparity in melanoma stage, tumor depth, and ulcerated tumors at diagnosis emphasizes the need for greater secondary prevention efforts among this group.