Pregnancy health in a multi-state U.S. population of systemically underserved patients and their children: PROMISE cohort design and baseline characteristics.

BACKGROUND: Gestational weight gain (GWG) is a routinely monitored aspect of pregnancy health, yet critical gaps remain about optimal GWG in pregnant people from socially marginalized groups, or with pre-pregnancy body mass index (BMI) in the lower or upper extremes. The PROMISE study aims to determine overall and trimester-specific GWG associated with the lowest risk of adverse birth outcomes and detrimental infant and child growth in these underrepresented subgroups. This paper presents methods used to construct the PROMISE cohort using electronic health record data from a network of community-based healthcare organizations and characterize the cohort with respect to baseline characteristics, longitudinal data availability, and GWG. METHODS: We developed an algorithm to identify and date pregnancies based on outpatient clinical data for patients 15 years or older. The cohort included pregnancies delivered in 2005-2020 with gestational age between 20 weeks, 0 days and 42 weeks, 6 days; and with known height and adequate weight measures needed to examine GWG patterns. We linked offspring data from birth records and clinical records. We defined study variables with attention to timing relative to pregnancy and clinical data collection processes. Descriptive analyses characterize the sociodemographic, baseline, and longitudinal data characteristics of the cohort, overall and within BMI categories. RESULTS: The cohort includes 77,599 pregnancies: 53% had incomes below the federal poverty level, 82% had public insurance, and the largest race and ethnicity groups were Hispanic (56%), non-Hispanic White (23%) and non-Hispanic Black (12%). Pre-pregnancy BMI groups included 2% underweight, 34% normal weight, 31% overweight, and 19%, 8%, and 5% Class I, II, and III obesity. Longitudinal data enable the calculation of trimester-specific GWG; e.g., a median of 2, 4, and 6 valid weight measures were available in the first, second, and third trimesters, respectively. Weekly rate of GWG was 0.00, 0.46, and 0.51 kg per week in the first, second, and third trimesters; differences in GWG between BMI groups were greatest in the second trimester. CONCLUSIONS: The PROMISE cohort enables characterization of GWG patterns and estimation of effects on child growth in underrepresented subgroups, ultimately improving the representativeness of GWG evidence and corresponding guidelines.

Treatment Strategies for Glioblastoma in the Elderly: What Should We Focus on Compared to Younger Patients.

(1) Background: Although the incidence of glioblastoma (GB) has a peak in patients aged 75-84 years, no standard treatment regimen for elderly patients has been established so far. The goal of this study was to analyze the outcome of GB patients ≥ 65 years to detect predictors with relevant impacts on overall survival (OS) and progression-free survival (PFS). (2) Methods: Medical records referred to our institution from 2006 to 2020 were analyzed. Adult GB patients with clinical data, postoperative MRI data, and ≥1 follow-up investigation after surgical resection were included. The complete cohort was divided into a younger (<65) and an elderly group (≥65 years). Multiple factors regarding OS and PFS were scanned using univariate and multivariable regression with p < 0.05. (3) Results: 1004 patients were included with 322 (61.0%) male individuals in the younger and 267 (56.1%) males in the older cohort. The most common tumor localization was frontal in both groups. Gross total resection (GTR) was the most common surgical procedure in both groups, followed by subtotal resection (STR) (145; 27.5%) in the younger group, and biopsy (156; 32.8%) in the elderly group. Multivariate analyses detected that in the younger cohort, MGMT promoter methylation and GTR were predictors for a longer OS, while MGMT methylation, GTR, and hypofractionated radiation were significantly associated with a longer OS in the elderly group. (4) Conclusions: Elderly patients benefit from surgical resection of GB when they show MGMT promoter methylation, undergo GTR, and receive hypofractionated radiation. Furthermore, MGMT methylation seems to be associated with a longer PFS in elderly patients. Further investigations are required to confirm these findings, especially within prospective radiation therapy studies and molecular examinations.

Insurance coverage and discontinuity during pregnancy: Frequency and associations documented in the PROMISE cohort.

OBJECTIVE: To describe insurance patterns and discontinuity during pregnancy, which may affect the experiences of the pregnant person: their timely access to care, continuity of care, and health outcomes. DATA SOURCES AND STUDY SETTING: Data are from the PROMISE study, which utilizes data from community-based health care organizations (CHCOs) (e.g., federally qualified health centers that serve patients regardless of insurance status or ability to pay) in the United States from 2005 to 2021. STUDY DESIGN: This descriptive study was a cohort utilizing longitudinal electronic health record data. DATA COLLECTION/EXTRACTION METHODS: Insurance type at each encounter was recorded in the clinical database and coded as Private, Public, and Uninsured. Pregnant people were categorized into one of several insurance patterns. We analyzed the frequency and timing of insurance changes and care utilization within each group. PRINCIPAL FINDINGS: Continuous public insurance was the most common insurance pattern (69.2%), followed by uninsured/public discontinuity (11.8%), with 6.4% experiencing uninsurance throughout the entirety of pregnancy. Insurance discontinuity was experienced by 16.6% of pregnant people; a majority of these reflect people transitioning to public insurance. Those with continuous public insurance had the highest frequency of inadequate prenatal care (19.5%), while those with all three types of insurance during pregnancy had the highest percentage of intensive prenatal care (16.5%). The majority (71.7%-81.2%) of those with a discontinuous pattern experienced a single insurance change. CONCLUSIONS: Insurance discontinuity and uninsurance are common within our population of pregnant people seeking care at CHCOs. Our findings suggest that insurance status should be regarded as a dynamic rather than a static characteristic during pregnancy and should be measured accordingly. Future research is needed to assess the drivers of perinatal insurance discontinuity and if and how these discontinuities may affect health care access, utilization, and birth outcomes.

Are we providing best-available care to newly diagnosed glioblastoma patients? Systematic review of phase III trials in newly diagnosed glioblastoma 2005-2022.

Background: Glioblastoma is the most aggressive primary brain cancer with a poor prognosis. Despite numerous studies in the past 17 years, effective treatment options for glioblastoma remain limited. In this study, we aimed to identify and compare phase III clinical trials for glioblastoma in terms of efficacy and baseline characteristics. Methods: A systematic literature search was conducted using PubMed and ClinicalTrials.gov to identify phase III clinical trials for glioblastoma in adult patients. The target population included adult patients aged 18 years and above (younger cohort) and patients ≥60 years of age (elderly cohort). The search results were screened based on predefined inclusion criteria, and the included trials were analyzed for their study design, baseline characteristics, and survival results. Results: Eleven trials met the inclusion criteria in the younger cohort. Of these, three reported a statistically significant improvement in overall survival (OS), including the EORTC/NCIC study (NCT00006353), EF-14 (NCT00916409), and CeTeG (NCT01149109). Of the 11 trials, eight were open-label randomized trials, including all of the positive ones, while three negative trials employed treatment blinding and a placebo control. The baseline characteristics of the trials [such as extent of resection, age, gender, and O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status] did not significantly differ between positive and negative trials. Isocitrate dehydrogenase (IDH) mutation status was analyzed in only two trials, with a small percentage of IDH-mutated tumors in each. Additionally, three more trials in the elderly cohort showed a statistically significant improvement of OS, the NOA-08 trial, the ISRCTN81470623-trial by Malmström et al. and NCT00482677-trial by Perry et al. Their baseline characteristics and implications are also analyzed. Conclusion: This analysis of phase III clinical trials for glioblastoma conducted since 2005 showed that the majority of trials did not result in a significant improvement in OS. Among the trials included in this analysis, only the EORTC/NCIC, EF-14, and CeTeG studies demonstrated a positive OS outcome in the younger cohort.

Impact of Health Insurance Patterns on Chronic Health Conditions Among Older Patients.

BACKGROUND: Patients have varying levels of chronic conditions and health insurance patterns as they become Medicare age-eligible. Understanding these dynamics will inform policies and reforms that direct capacity and resources for primary care clinics to care for these aging patients. This study 1) determined changes in chronic condition rates following Medicare age eligibility among patients with different insurance patterns and 2) estimated the number of chronically ill patients who remain inadequately insured post-Medicare eligibility among patients receiving care in community health centers. METHOD: We used retrospective electronic health record data from 45,527 patients aged 62 to 68 from 990 community health centers in 25 states in 2014 to 2019. Insurance patterns (continuously insured, continuously uninsured, uninsured/discontinuously insured who gained insurance after age 65, lost insurance after age 65, discontinuously insured) and diagnosis of chronic conditions were defined at each visit pre- and post-Medicare eligibility. Difference-in-differences Poisson GEE models estimated changes of chronic condition rates by insurance groups pre- to post-Medicare age eligibility. RESULTS: Post-Medicare eligibility, 72% patients were continuously insured, 14% gained insurance; and 14% were uninsured or discontinuously insured. The prevalence of multimorbidity (≥2 chronic conditions) was 77%. Those who gained insurance had a significantly larger increase in the rate of documented chronic conditions from pre- to post-Medicare (DID: 1.06, 95%CI:1.05-1.07) compared with the continuously insured group. CONCLUSIONS: Post-Medicare age eligibility, a significant proportion of patients were diagnosed with new conditions leading to high burden of disease. One in 4 older adults continue to have inadequate health care coverage in their older age.

Telemedicine in Neuro-Oncology-An Evaluation of Remote Consultations during the COVID-19 Pandemic.

In order to minimize the risk of infections during the COVID-19 pandemic, remote video consultations (VC) experienced an upswing in most medical fields. However, telemedicine in neuro-oncology comprises unique challenges and opportunities. So far, evidence-based insights to evaluate and potentially customize current concepts are scarce. To fill this gap, we analyzed >3700 neuro-oncological consultations, of which >300 were conducted as VC per patients' preference, in order to detect how both patient collectives distinguished from one another. Additionally, we examined patients' reasons, suitable/less suitable encounters, VC's benefits and disadvantages and future opportunities with an anonymized survey. Patients that participated in VC had a worse clinical condition, higher grade of malignancy, were more often diagnosed with glioblastoma and had a longer travel distance (all p < 0.01). VC were considered a fully adequate alternative to face-to-face consultations for almost all encounters that patients chose to participate in (>70%) except initial consultations. Most participants preferred to alternate between both modalities rather than participate in one alone but preferred VC over telephone consultation. VC made patients feel safer, and participants expressed interest in implementing other telemedicine modalities (e.g., apps) into neuro-oncology. VC are a promising addition to patient care in neuro-oncology. However, patients and encounters should be selected individually.

Correlation between Targeted qPCR Assays and Untargeted DNA Shotgun Metagenomic Sequencing for Assessing the Fecal Microbiota in Dogs.

DNA shotgun sequencing is an untargeted approach for identifying changes in relative abundances, while qPCR allows reproducible quantification of specific bacteria. The canine dysbiosis index (DI) assesses the canine fecal microbiota by using a mathematical algorithm based on qPCR results. We evaluated the correlation between qPCR and shotgun sequencing using fecal samples from 296 dogs with different clinical phenotypes. While significant correlations were found between qPCR and sequencing, certain taxa were only detectable by qPCR and not by sequencing. Based on sequencing, less than 2% of bacterial species (17/1190) were consistently present in all healthy dogs (n = 76). Dogs with an abnormal DI had lower alpha-diversity compared to dogs with normal DI. Increases in the DI correctly predicted the gradual shifts in microbiota observed by sequencing: minor changes (R = 0.19, DI < 0 with any targeted taxa outside the reference interval, RI), mild-moderate changes (R = 0.24, 0 < DI < 2), and significant dysbiosis (R = 0.54, 0.73, and 0.91 for DI > 2, DI > 5, and DI > 8, respectively), compared to dogs with a normal DI (DI < 0, all targets within the RI), as higher R-values indicated larger dissimilarities. In conclusion, the qPCR-based DI is an effective indicator of overall microbiota shifts observed by shotgun sequencing in dogs.

Feasibility and tolerability of trofosfamide and etoposide in progressive glioblastoma.

Background: Standard of care treatment options at glioblastoma relapse are still not well defined. Few studies indicate that the combination of trofosfamide plus etoposide may be feasible in pediatric glioblastoma patients. In this retrospective analysis, we determined tolerability and feasibility of combined trofosfamide plus etoposide treatment at disease recurrence of adult glioblastoma patients. Methods: We collected clinicopathological data from adult progressive glioblastoma patients treated with the combination of trofosfamide and etoposide for more than four weeks (one course). A cohort of patients receiving empiric treatment at the investigators' discretion balanced for tumor entity and canonical prognostic factors served as control. Results: A total of n = 22 progressive glioblastoma patients were eligible for this analysis. Median progression-free survival (3.1 vs 2.3 months, HR: 1.961, 95% CI: 0.9724-3.9560, P = .0274) and median overall survival (9.0 vs 5.7 months, HR: 4.687, 95% CI: 2.034-10.800, P = .0003) were significantly prolonged compared to the control cohort (n = 17). In a multivariable Cox regression analysis, treatment with trofosfamide plus etoposide emerged as a significant prognostic marker regarding progression-free and overall survival. We observed high-grade adverse events in n = 16/22 (73%) patients with hematotoxicity comprising the majority of adverse events (n = 15/16, 94%). Lymphopenia was by far the most commonly observed hematotoxic adverse event (n = 11/15, 73%). Conclusions: This study provides first indication that the combination of trofosfamide plus etoposide is safe in adult glioblastoma patients. The observed survival outcomes might suggest potential beneficial effects. Our data provide a reasonable rationale for follow-up of a larger cohort in a prospective trial.

Trajectories of Chronic Disease and Multimorbidity Among Middle-aged and Older Patients at Community Health Centers.

Importance: Health-related consequences of multimorbidity (≥2 chronic diseases) are well documented. However, the extent and rate of accumulation of chronic diseases among US patients seeking care in safety-net clinics are not well understood. These insights are needed to enable clinicians, administrators, and policy makers to mobilize resources for prevention of disease escalations in this population. Objectives: To identify the patterns and rate of chronic disease accumulation among middle-aged and older patients seeking care in community health centers, as well as any sociodemographic differences. Design, Setting, and Participants: This cohort study used electronic health record data from January 1, 2012, to December 31, 2019, on 725 107 adults aged 45 years or older with 2 or more ambulatory care visits in 2 or more distinct years at 657 primary care clinics in the Advancing Data Value Across a National Community Health Center network in 26 US states. Statistical analysis was performed from September 2021 to February 2023. Exposures: Race and ethnicity, age, insurance coverage, and federal poverty level (FPL). Main Outcomes and Measures: Patient-level chronic disease burden, operationalized as the sum of 22 chronic diseases recommended by the Multiple Chronic Conditions Framework. Linear mixed models with patient-level random effects adjusted for demographic characteristics and ambulatory visit frequency with time interactions were estimated to compare accrual by race and ethnicity, age, income, and insurance coverage. Results: The analytic sample included 725 107 patients (417 067 women [57.5%]; 359 255 [49.5%] aged 45-54 years, 242 571 [33.5%] aged 55-64 years, and 123 281 [17.0%] aged ≥65 years). On average, patients started with a mean (SD) of 1.7 (1.7) morbidities and ended with 2.6 (2.0) morbidities over a mean (SD) of 4.2 (2.0) years of follow-up. Compared with non-Hispanic White patients, patients in racial and ethnic minoritized groups had marginally lower adjusted annual rates of accrual of conditions (-0.03 [95% CI, -0.03 to -0.03] for Spanish-preferring Hispanic patients; -0.02 [95% CI, -0.02 to -0.01] for English-preferring Hispanic patients; -0.01 [95% CI, -0.01 to -0.01] for non-Hispanic Black patients; and -0.04 [95% CI, -0.05 to -0.04] for non-Hispanic Asian patients). Older patients accrued conditions at higher annual rates compared with patients 45 to 50 years of age (0.03 [95% CI, 0.02-0.03] for 50-55 years; 0.03 [95% CI, 0.03-0.04] for 55-60 years; 0.04 [95% CI, 0.04-0.04] for 60-65 years; and 0.05 [95% CI, 0.05-0.05] for ≥65 years). Compared with those with higher income (always ≥138% of the FPL), patients with income less than 138% of the FPL (0.04 [95% CI, 0.04-0.05]), mixed income (0.01 [95% CI, 0.01-0.01]), or unknown income levels (0.04 [95% CI, 0.04-0.04]) had higher annual accrual rates. Compared with continuously insured patients, continuously uninsured and discontinuously insured patients had lower annual accrual rates (continuously uninsured, -0.003 [95% CI, -0.005 to -0.001]; discontinuously insured, -0.004 [95% CI, -0.005 to -0.003]). Conclusions and Relevance: This cohort study of middle-aged patients seeking care in community health centers suggests that disease accrued at high rates for patients' chronological age. Targeted efforts for chronic disease prevention are needed for patients near or below the poverty line.

A six-month prospective, randomised, double-blinded, placebo-controlled, crossover, dietary trial design to investigate the potential of psychobiotics on seizure semiology and comorbidities in canine epilepsy: study protocol.

BACKGROUND: Epilepsy is the most common chronic neurological disease in dogs. More than two-thirds of these patients suffer from associated behavioural comorbidities. The latter could have their origin in partially overlapping pathomechanisms, with the intestinal microbiome as a potential key link between them. The current arsenal of drugs for epilepsy management remains limited. Most canine patients continue to have seizures despite treatment and the occurrence of comorbidities is not sufficiently addressed, limiting quality of life of affected dogs and owners. Therefore, novel additional epilepsy management options are urgently needed. The microbiome-gut-brain axis may serve as a new target for the development of innovative multimodal therapeutic approaches to overcome current shortcomings in epilepsy management. METHODS: A six-month prospective, randomised, double-blinded, placebo-controlled, crossover, dietary trial was designed to investigate the potential of the psychobiotic Bifidobacterium longum on behavioural comorbidities in canine epilepsy. Seizure semiology will be evaluated as a secondary outcome measure. Thirty-four privately owned dogs are planned to be included in the ongoing study meeting the following inclusion criteria: Dogs displaying increased anxiety/fear behaviour since the start of the idiopathic epilepsy. Tier II confidence level of the International Veterinary Epilepsy Task Force for the diagnosis of idiopathic epilepsy, with a maximum seizure interval of 3 month and a minimum of three generalised seizures within that period and chronically treated with at least one antiseizure drug without improvement in seizure frequency Each dog will receive the allocated supplement (probiotic vs. placebo) alongside its normal diet for a 3-month period. After a three-week wash out period, the second phase starts by administering the respective other supplement for another 3 months. DISCUSSION: The current study considers modern high-quality standards for epilepsy medication trials. Common biasing effects should be limited to a possible minimum (regression-to-the mean effect, placebo effect, observer effect), ensuring a high validity and accuracy of the acquired results, thus enabling a representative nature of the efficacy of Bifidobacterium longum as add-on supplement for dogs suffering from epilepsy and its comorbidities. This publication should provide a description of the study procedure and data acquisition methods, including prognosed statistical analysis.

Urinary neurotransmitter analysis and canine behavior assessment.

Behavioral problems are highly prevalent in domestic dogs, negatively affecting the quality of life of dogs and their owners. In humans and dogs, neuropsychological or neurobehavioral disorders can be associated with deviations in various neurotransmitter systems. Previous evidence has revealed correlations between urinary neurotransmitters and various behavioral disorders; however, a causal relationship has not yet been conclusively demonstrated. Non-invasive urinary neurotransmitter analysis may identify specific biomarkers, which enable a more differentiated assessment of canine behavioral disorders in the future and contribute to more effective neuromodulatory treatment decisions and monitoring. This approach could offer new insights into underlying pathomechanisms of canine neurobehavioral disorders. This study assessed urinary neurotransmitter levels and the descriptive behavior profile of 100 dogs using established rating scales (Canine Behavioral Assessment and Research Questionnaire, Attention Deficit Hyperactivity Disorder Rating Scale, Dog Personality Questionnaire, Canine Cognitive Dysfunction Rating Scale), and explored relationships between these variables. No correlation was found between urinary neurotransmitters and the assessed behavior profiles; however, age-, sex- and neuter-related influences were identified. The lack of correlation could be explained by the many confounding factors influencing both behavior and urinary neurotransmitter excretion, including age, sex and neuter status effects, and methodological issues e.g., low discriminatory power between anxiety and aggression in the descriptive behavior evaluation. Urinary neurotransmitter testing could not be validated as a tool for canine behavior evaluation in this study. However, reliable assessment methods with low susceptibility to human biases could be valuable in the future to support behavioral-phenotype diagnoses.

Precision neuro-oncology: a pilot analysis of personalized treatment in recurrent glioma.

PURPOSE: When brain cancer relapses, treatment options are scarce. The use of molecularly matched targeted therapies may provide a feasible and efficacious way to treat individual patients based on the molecular tumor profile. Since little information is available on this strategy in neuro-oncology, we retrospectively analyzed the clinical course of 41 patients who underwent advanced molecular testing at disease relapse. METHODS: We performed Sanger sequencing, targeted next generation sequencing, and immunohistochemistry for analysis of potential targets, including programmed death ligand 1, cyclin D1, phosphorylated mechanistic target of rapamycin, telomerase reverse transcriptase promoter mutation, cyclin-dependent kinase inhibitor 2A/B deletion, or BRAF-V600E mutation. In selected patients, whole exome sequencing was conducted. RESULTS: The investigation included 41 patients, of whom 32 had isocitrate dehydrogenase (IDH) wildtype glioblastoma. Molecular analysis revealed actionable targets in 31 of 41 tested patients and 18 patients were treated accordingly (matched therapy group). Twenty-three patients received molecularly unmatched empiric treatment (unmatched therapy group). In both groups, 16 patients were diagnosed with recurrent IDH wildtype glioblastoma. The number of severe adverse events was comparable between the therapy groups. Regarding the IDH wildtype glioblastoma patients, median progression-free survival (mPFS) and median overall survival (mOS) were longer in the matched therapy group (mPFS: 3.8 versus 2.0 months, p = 0.0057; mOS: 13.0 versus 4.3 months, p = 0.0357). CONCLUSION: These encouraging data provide a rationale for molecularly matched targeted therapy in glioma patients. For further validation, future study designs need to additionally consider the prevalence and persistence of actionable molecular alterations in patient tissue.

Impact of the Affordable Care Act Medicaid Expansion on Weight Loss among Community Health Center Patients with Obesity.

Context: Obesity affects over 40% of the US population and is linked to multiple preventable health conditions which can cause premature morbidity and mortality. Weight loss of at least 5% in patients with obesity reduces their risk of comorbid conditions and leads to improvement in some conditions, such as diabetes. Patients with obesity from underserved populations are less likely to access primary and preventive care services. The Affordable Care Act (ACA) improved access to care, which may in turn improve access to obesity prevention and treatment and assist with weight loss. Objective: Assess whether the proportion of patients with a weight loss ≥5% was higher in states that expanded Medicaid relative to non-expansion states among patients with obesity receiving care in community health centers (CHCs) which provide health care to underserved patients. Study Design: Retrospective observational cohort study. Setting: Electronic health record data from the ADVANCE (Advancing Data Value Across a National Community Health Center) clinical research network, during years 2012-2017. Population Studied: Patients from 346 CHCs age 19-64 with a body mass index of ≥ 30 kg/m2 during the pre-ACA period (n=34,027). Outcome measures: Proportion of patients with weight loss >5% (WL5+) from pre- to post-ACA. Medicaid expansion status (expansion vs. non-expansion states) stratified by pattern of insurance (uninsured, continuously insured, newly insured, discontinuously insured) and race and ethnicity. Results: The proportion of patients with WL5+ for newly insured patients was greater in expansion (26%) than non-expansion states (20%) (χ2=9.75, p=0.002). Among newly insured patients, Hispanic (22%) and Black (29%) patients residing in expansion states, had larger proportion of patients with WL5+ than those in non-expansion states (20% and 18%, respectively). No differences were observed among non-Hispanic White patients (expansion 28% vs non-expansion 27%). Conclusions: The findings suggest greater improvement in weight management among patients residing in expansion states than those in non-expansion states, especially among racial and ethnic minorities receiving care in CHCs.

The role of nutrition in canine idiopathic epilepsy management: Fact or fiction?

In the last decade, nutrition has gained interest in the management of canine idiopathic epilepsy (IE) based on growing scientific evidence. Diets can serve their functions through many pathways. One potential pathway includes the microbiota-gut-brain axis, which highlights the relationship between the brain and the intestines. Changing the brain's energy source and a number of dietary sourced anti-inflammatory and neuroprotective factors appears to be the basis for improved outcomes in IE. Selecting a diet with anti-seizure effects and avoiding risks of proconvulsant mediators as well as interference with anti-seizure drugs should all be considered in canine IE. This literature review provides information about preclinical and clinical evidence, including a systematic evaluation of the level of evidence, suggested mechanism of action and interaction with anti-seizure drugs as well as pros and cons of each potential dietary adaptation in canine IE.

First multicentric real-life experience with the combination of CCNU and temozolomide in newly diagnosed MGMT promoter methylated IDH wildtype glioblastoma.

Background: The randomized phase 3 CeTeG/NOA-09 trial assessed whether CCNU plus temozolomide was superior to temozolomide alone in newly diagnosed MGMT promoter methylated glioblastoma patients. Survival was significantly improved from 31.4 months (temozolomide) to 48.1 months (CCNU plus temozolomide). In view of this encouraging data, we assessed safety and efficacy of this regimen under real-life conditions. Methods: We retrospectively collected clinical and radiographic data from adult newly diagnosed MGMT promoter methylated IDH wildtype glioblastoma patients from five neuro-oncology centers in Germany. For inclusion in our analysis, treatment with CCNU and temozolomide had to be performed for at least six weeks (one course). Results: Seventy patients were included. Median progression-free survival was 14.4 months and median overall survival 33.8 months. Patients with TTFields treatment for at least 8 weeks and CCNU plus temozolomide (n = 22, 31%) had a prolonged progression-free survival compared to those with TTFields treatment for less than eight weeks (n = 48, 69%) (21.5 versus 11.2 months; P = .0105). In a multivariable Cox regression analysis, TTFields treatment for eight weeks or longer together with CCNU plus temozolomide and a Karnofsky performance score ≥ 90% were independent prognostic factors for progression-free and overall survival. Pseudoprogression occurred in n = 16 (33%) of investigated n = 49 (70%) patients. In n = 31 (44%) patients high-grade hematotoxicity was observed. Conclusions: The results from this multicentric trial indicate that-under real-life conditions-toxicity and survival estimates are comparable to the CeTeG/NOA-09 trial. TTFields therapy for at least eight weeks in combination with this regimen was independently associated with prolonged survival.

Urinary Neurotransmitter Patterns Are Altered in Canine Epilepsy.

Epilepsy is the most common chronic neurological disease in humans and dogs. Epilepsy is thought to be caused by an imbalance of excitatory and inhibitory neurotransmission. Intact neurotransmitters are transported from the central nervous system to the periphery, from where they are subsequently excreted through the urine. In human medicine, non-invasive urinary neurotransmitter analysis is used to manage psychological diseases, but not as yet for epilepsy. The current study aimed to investigate if urinary neurotransmitter profiles differ between dogs with epilepsy and healthy controls. A total of 223 urine samples were analysed from 63 dogs diagnosed with idiopathic epilepsy and 127 control dogs without epilepsy. The quantification of nine urinary neurotransmitters was performed utilising mass spectrometry technology. A significant difference between urinary neurotransmitter levels (glycine, serotonin, norepinephrine/epinephrine ratio, ɤ-aminobutyric acid/glutamate ratio) of dogs diagnosed with idiopathic epilepsy and the control group was found, when sex and neutering status were accounted for. Furthermore, an influence of antiseizure drug treatment upon the urinary neurotransmitter profile of serotonin and ɤ-aminobutyric acid concentration was revealed. This study demonstrated that the imbalances in the neurotransmitter system that causes epileptic seizures also leads to altered neurotransmitter elimination in the urine of affected dogs. Urinary neurotransmitters have the potential to serve as valuable biomarkers for diagnostics and treatment monitoring in canine epilepsy. However, more research on this topic needs to be undertaken to understand better the association between neurotransmitter deviations in the brain and urine neurotransmitter concentrations in dogs with idiopathic epilepsy.

Title X Improved Access To Most Effective And Moderately Effective Contraception In US Safety-Net Clinics, 2016-18.

Community health centers are a crucial source of health care for reproductive-age women. Some community health centers receive funding from the federal Title X program, which provides funding for family planning services for low-income women. We describe the provision of the most effective (intrauterine devices and implants) and moderately effective (short-acting hormonal methods) contraceptive methods in a large network of 384 community health center clinics across twenty states in 2016-18. Title X clinics provided more most and moderately effective contraception at all time points and for all age groups (adolescent, young adult, and adult). They provided 52 percent more of the most effective contraceptives to women at risk for pregnancy than clinics not funded by Title X. This finding was especially notable for adolescents (58 percent more). Title X clinics play a key role in access to effective contraception across the US safety net. Strengthening the Title X program should continue to be a policy priority for public health for the Biden-Harris administration.

Prediction of Short and Long Survival after Surgery for Breast Cancer Brain Metastases.

Background: Brain metastases requiring surgical treatment determine the prognosis of patients with breast cancer. We aimed to develop the scores for the prediction of short (<6 months) and long (≥3 years) survival after BCBM surgery. Methods: Female patients with BCBM surgery between 2008 and 2019 were included. The new scores were constructed upon independent predictors for short and long postoperative survival. Results: In the final cohort (n = 95), 18 (18.9%) and 22 (23.2%) patients experienced short and long postoperative survival, respectively. Breast-preserving surgery, presence of multiple brain metastases and age ≥ 65 years at breast cancer diagnosis were identified as independent predictors of short postoperative survival. In turn, positive HER2 receptor status in brain metastases, time interval ≥ 3 years between breast cancer and brain metastases diagnosis and KPS ≥ 90% independently predicted long survival. The appropriate short and long survival scores showed higher diagnostic accuracy for the prediction of short (AUC = 0.773) and long (AUC = 0.775) survival than the breast Graded Prognostic Assessment score (AUC = 0.498/0.615). A cumulative survival score (total score) showed significant association with overall survival (p = 0.001). Conclusion: We identified predictors independently impacting the prognosis after BCBM surgery. After external validation, the presented scores might become useful tools for the selection of proper candidates for BCBM surgery.