Changes In Disease Course Research Articles

Serum tumor markers and outcomes in lung cancer patients with brain metastases: a retrospective longitudinal cohort study.

Serum tumor markers (STMs) are recommended for cancer diagnosis and surveillance. However, their role in lung cancer with brain metastases (BM) is not yet clear. We aim to analyze the roles of baseline levels of STMs or ongoing STM surveillance on survival. This retrospective longitudinal cohort study included 1,169 lung cancer patients with BM. The STM data during disease course were collected. Distinct trajectory groups were identified using the latent class growth mixed model (LCGMM). The roles of STMs on survival were further analyzed using Kaplan-Meier analysis and Cox proportional hazard models. Serum levels of cytokeratin-19 fragment (CYFRA21-1) (P<0.001), carcinoembryonic antigen (CEA) (P=0.005) and neuron-specific enolase (NSE) (P<0.001) at baseline exhibited significant correlation with overall survival (OS) of patients with BM, serving as independent prognostic factors. Further analysis indicated that baseline CYFRA21-1, CEA, NSE as well as status of key driver genes were independent prognostic factors in non-small cell lung cancer (NSCLC) patients with BM, while for small cell lung cancer (SCLC) patients with BM, baseline NSE and receiving chemotherapy show independent correlations with survival. Furthermore, we delineated the dynamic trajectories of STMs based on changes in disease course. More specifically, compared to those showing a baseline-high trend in CEA levels, the survival of patients with either persistently-rising or consistently normal levels seemed to be more promising. For CYFRA21-1, both early-rising and later-rising trends were observed, indicating a prognosis inferior to that of individuals with normal-level trajectory. Likewise, for NSE, patients with persistently-rising or persistently-descending trends showed no significantly survival difference. However, in comparison with the status of driver genes, receiving radiotherapy and targeted therapy, the dynamic changes in STM levels lacked independent prognostic significance. Further analysis indicated that among BM patients lacking key driver genes, NSE trajectory (P<0.05), CYFRA21-1 trajectory (P<0.05) and receiving chemotherapy (P<0.001) were independent prognostic factors. Baseline levels of serum CYFRA21-1, CEA and NSE, as well as status of key driver genes are recommended for evaluating BM patients' outcome. Dynamic changes of STMs during disease course were not significantly associated with the final outcome of BM patients.

Clinical Features and Survival Analysis of Lupus Nephritis among Patients with Systemic Lupus Erythematosus: A Three-Decade-Long Retrospective Cohort Study.

Background/Objectives: Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). The aim of our retrospective cohort study was to compare the clinical characteristics, therapy, survival, causes of death, and prognostic factors of LN and non-LN lupus patients. Moreover, we compared a wide spectrum of clinical data of LN patients diagnosed before and since 2005 to determine any changes in disease course and outcomes. Methods: We assessed the clinical and laboratory data of 384 SLE patients, out of whom, 127 patients were diagnosed with LN between 1990 and 2020. Results: Based on our observations, discoid LE, subacute cutaneous LE, antiphospholipid syndrome, Sjögren's syndrome, and rheumatoid arthritis were more common in non-LN patients, while anemia and anti-RNP positivity were more frequent in LN patients. Development of LN did not affect survival rates; male sex and presence of APS were negative prognostic parameters in the non-LN group while achieving remission was a positive prognostic factor in both groups. Death caused by sepsis was more prevalent in the LN group. Serositis and neurological manifestations occurred less frequently in LN patients diagnosed after 2005. The use of mycophenolate mofetil became more common, and the cumulative corticosteroid dose decreased. The SLICC Damage Index score also decreased. Conclusions: Our study demonstrated that the disease course has changed in recent years, and the main therapeutic goal in both SLE and lupus nephritis should be to achieve remission because this significantly improves long-term prognosis and patient survival.

The association of menopausal hormone levels with progression-related biomarkers in multiple sclerosis

BackgroundMultiple sclerosis (MS) progression coincides temporally with menopause. However, it remains unclear whether the changes in disease course are related to the changes in reproductive hormone concentrations. We assessed the association of menopausal hormonal levels with progression-related biomarkers of MS and evaluated the changes in serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels during menopausal hormone therapy (MHT) in a prospective baseline-controlled design. MethodsThe baseline serum estradiol, follicle stimulating hormone, and luteinizing hormone levels were measured from menopausal women with MS (n = 16) and healthy controls (HC, n = 15). SNfL and sGFAP were measured by single-molecule array. The associations of hormone levels with sNfL and sGFAP, and with Expanded Disability Status Scale (EDSS) and lesion load and whole brain volumes (WBV) in MRI were analyzed with Spearman's rank correlation and age-adjusted linear regression model. Changes in sNfL and sGFAP during one-year treatment with estradiol hemihydrate combined with cyclic dydrogesterone were assessed with Wilcoxon Signed Ranks Test. ResultsIn MS group, baseline estradiol had a positive correlation with WBV in MRI and an inverse correlation with lesion load, sNfL and sGFAP, but no correlation with EDSS. The associations of low estradiol with high sGFAP and low WBV were independent of age. During MHT, there was no significant change in sNfL and sGFAP levels in MS group while in HC, sGFAP slightly decreased at three months but returned to baseline at 12 months. ConclusionOur preliminary findings suggest that low estradiol in menopausal women with MS has an age-independent association with more pronounced brain atrophy and higher sGFAP and thus advanced astrogliosis which could partially explain the more rapid progression of MS after menopause. One year of MHT did not alter the sGFAP or sNfL levels in women with MS.

Treatment Patterns and Outcomes of Patients with Acute Myeloid Leukemia (AML) from 2013 to 2022: A Connect ® Myeloid Registry Study

Introduction There has been a rapid evolution in diagnostic and management evaluation for AML, associated with the introduction of new therapies, some of which target specific mutations, over the past decade. The Connect ® Myeloid Registry (NCT01688011) is a multicenter, prospective, observational cohort study that began enrollment in December 2013 and represents a rich source of information to evaluate changes in disease course and outcomes over time in patients with myeloid diseases. We evaluated 10-year longitudinal data from patients with AML treated in real-world clinical practice at community and academic institutions to understand the evolution of diagnosis and treatment of patients with this myeloid condition. Methods Patients in the AML cohort were ≥ 55 years of age and newly diagnosed with AML according to the 2008 revised World Health Organization criteria and were grouped by year of diagnosis: 2013-2016 (Group 1; before commercial availability of numerous novel therapies including venetoclax, midostaurin, ivosidenib, enasidenib, gemtuzumab ozogamicin, and others), and 2017-2022 (Group 2; after availability of new therapies). Baseline demographic and clinical characteristics, treatment patterns, and outcomes were evaluated by group. Overall survival (OS) from the date of diagnosis was estimated by the Kaplan-Meier method. Results A total of 773 patients with AML (Group 1, n = 292; Group 2, n = 481) were assessed. Median (range) age was 70.0 years (55.0-91.0) in Group 1, and 71.0 years (55.0-97.0) in Group 2. Median OS was 11.0 months (95% confidence interval [CI]: 9.0-14.0) in Group 1, and 16.0 months (13.0-18.0) in Group 2 ( P = 0.039; Figure). A higher percentage of patients in Group 2 survived to 60 months compared with Group 1 ( Figure). Improved survival over time was primarily observed in patients &amp;lt; 75 years of age at diagnosis; median (95% CI) OS among patients &amp;lt; 75 years of age increased over time from 14.0 months (11.0-17.0) in Group 1 to 20.0 months (17.0-24.0) in Group 2 ( P = 0.022) but remained unchanged over time among patients ≥ 75 years of age (9.0 months [6.0-10.0] in Group 1; 9.0 months [6.0-13.0] in Group 2; P = NS). Rates of transplant increased significantly over time for younger patients; among those &amp;lt; 75 years of age at diagnosis, 45/201 (22%) in Group 1 received a transplant, compared with 99/318 (31%) in Group 2( P = 0.035). The proportion of patients receiving molecular testing increased over time from 68.8% in Group 1 to 86.9% in Group 2. The mean (standard deviation) number of mutations tested among those who underwent molecular testing also increased over time, from 6.1 (5.9) in Group 1 to 11.8 (7.4) in Group 2. Longer median (95% CI) OS was observed in patients who received molecular testing compared with those who did not: 14.0 months (11.0-17.0) versus 9.0 months (7.0-11.0) in Group 1; 16.0 months (13.0-19.0) versus 13.0 months (6.0-17.0) in Group 2. The proportion of patients receiving first-line treatment with intensive chemotherapy (IC) regimens was similar in the 2 time periods (Group 1, 51.0%; Group 2, 47.1%). Among patients not receiving IC, those in Group 2 increasingly received targeted therapies and venetoclax-based regimens and less-frequent low-intensity chemotherapy and supportive care. Conclusions In the AML cohort of Connect ® Myeloid, one of the longest-running US registries of myeloid diseases, we observed that patient characteristics at diagnosis were similar from 2013-2022. A statistically significant increase in median OS was observed over time. The increased rate of transplant, higher rates of molecular testing, and uptake of novel, targeted, treatments may have contributed to the improvement in survival. These results demonstrate the need for long-running, prospective observational studies to continue to understand rapidly changing treatment algorithms, combinations, and outcomes in AML.

P629 Evolution of disease phenotype, time to biological therapy and medium-, long-term surgery rates in Crohn’s disease patients in Western Hungary – a population-based study between 2007–2018, data from the Veszprem county cohort

Abstract Background The number of prospective population-based studies evaluating the natural disease course and surgical outcomes of Crohn’s disease(CD) are still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD population-based cohort with a follow-up of the incidence and disease course of IBD since 1977. Our aim was to evaluate disease course by examining progression in disease phenotype, time to biological therapy and surgery rates in a prospective population-based database from Veszprem Province, including incident CD patients diagnosed between January1,2007 and December31,2018. Methods Data of 421 incident CD patients were analyzed(male/female:237/184; median age at diagnosis:29 years(y)[IQR: 21–42]). Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. The mean length of follow-up was 8.53y(SD: 3.3). Probability of medium-, long-term change in disease course and surgical outcomes were analyzed. Results Disease location was ileal(L1), colonic(L2) in and ileo-colonic(L3) in 29.7%/24.5%/45.8% of patients at diagnosis. At the end of follow-up(8.53y), disease location was 27.1%/22.8%/50.1%(L1/L2/L3). The proportion of patients with upper gastrointestinal manifestation remained stable(7.6% and 8.1%), while perianal disease increased from 13.5% to 19% by the end of follow-up. Disease behavior at diagnosis was luminal(B1) in 62.5% of the patients. The probability of disease behavior progression from luminal into stenosing or penetrating phenotype was 11.9%(SE:1.7) at 3 years, 13.2%(SE:1.7) at 5 years and 17.6%(SE:1.7) at 10 years.Figure 1. The Probability of receiving biological therapy after diagnosis was 20.9%(SE:2.0) at 5 years and 28.8%(SE:2.0) at 10 years in this cohort. Overall resective surgery rate was 29.5% in the total population, while perianal surgery rate was 31.3% in patients with perianal disease at the end of follow-up. The probability of resective surgery was 20.7%(SE:2.0) at 1 year, 26.1%(SE:2.2) at 5 years and 30.7%(SE:2.4) at 10 years.Figure 2. For the probability of first perianal surgery among patients with perianal disease see Figure 3. Conclusion The probability of progression in disease behavior was lower compared to data from previous decades and similar to results from recent pan-European population-based data.(Burisch 2018, JCC). One-year surgery rates after diagnosis were considerably higher compared to previous data from our cohort or compared to Western and Northern European centers.(Lakatos 2011, IBD). Medium-term(5y) surgery rates were similar(~20%) compared to recent Hungarian and European data, while long-term(10y) rates decreased compared to data from previous decades.(Lakatos 2011,IBD; Lakatos 2012,AJG).

P658 Evolution of disease phenotype, time to biological therapy and medium-, long-term colectomy rates in Ulcerative Colitis patients in Western Hungary – a population-based study between 2007–2018, data from the Veszprem county cohort

Abstract Background The number of prospective population-based studies evaluating the natural disease course and surgical outcomes of ulcerative colitis (UC) are still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD population-based cohort with a follow-up of the incidence and disease course of IBD since 1977. Our aim was to evaluate disease course by examining progression in disease phenotype, time to biological therapy and colectomy rates in a prospective population-based database from Veszprem Province, including incident UC patients diagnosed between January 1, 2007 and December 31, 2018. Methods Data of 467 incident UC patients were analyzed (male/female: 236/1231; median age at diagnosis: 36 years(y) [IQR: 25–54]). Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. The mean length of follow-up was 8.34y (SD: 3.5). Disease phenotype was evaluated based on the Montreal classification. Probability of medium-, long-term change in disease course and surgical outcomes were analyzed using Kaplan–Meier survival analysis. Results Disease extension was proctitis (E1), left sided colitis (E2), and extensive colitis (E3) in 22.3%/ 43.9%/ 33.8% of patients at diagnosis. The probability of disease progression into more extensive phenotype was 6.9% (SE:1.2) at 3 years, 8.3% (SE:1.3) at 5 years and 11.3% (SE:1.6) at 10 years. Figure 1. The Probability of receiving biological therapy after diagnosis was 9.9% (SE:1.4) at 3 years, 13.9% (SE:1.6) at 5 years and 17.8% (SE:2.0) at 10 years in this cohort. Overall colectomy rate was 4.1% in the total population at the end of follow-up. The probability of colectomy was 1.5% (SE:0.6) at 1 year, 3.6% (SE:0.9) at 5 years and 4.4% (SE:1.0) at 10 years in Kaplan-Meier analysis. Figure 2. Conclusion The probability of progression in disease extent was low overall, similar to results from recent pan-European population-based data. (Burisch 2019, JCC). Medium- and long-term colectomy rates were lower compared to Western European centers, but somewhat higher compared to our previous data from the Veszprem cohort (2002–2006). (Lakatos 2011, IBD).

Herpes zoster post covid-19 vaccination

Aim: To find out association of herpes zoster and changes in disease course like incidence of post-herpetic neuralgia with Covid-19 vaccination. Study design: Cross-sectional, observational study. Place and duration of study: Outpatient Department of Dermatology, CMH and PEMH Rawalpindi from 1st January 2021 to 30th September 2021. Methodology: Seventy three patients presenting with herpes zoster selected by convenience sampling after their verbal and written consent. Demographics, Covid-19 vaccination history, type of vaccination, dermatome effected, co-morbids and presence of post herpetic neuralgia were recorded in them. Results: Mean age of participants was 48.09±15.73 years with 50 (68.5%) were males and 23 (31.5%) were females. 33 (45.2%) were vaccinated and 36 (49.3%) were non-vaccinated against covid-19. Maximum patients were vaccinated with Sinopharm i.e. 19(57.6%).8 (24.2%) patients developed the lesions after first dose and 25(75.8%) after 2nd dose of vaccination. Conclusion: Herpes zoster risk is increased with covid-19 vaccination. Key words: Herpes Zoster, Covid-19 vaccination

ONC 201 PRACTICE IN DIFFUSE MIDLINE GLIOMA (H3K27M MUTANT)

Diffuse Midline Gliomas (DMG), H3 K27M-mutant have the poorest prognosis among all pediatric high-grade gliomas, with a median survival of 9-11 months. Although radiotherapy (RT) is standard treatment for these tumors, unfortunately there has been no approved and effective treatment which completely diminishes the tumor yet. In our clinic, we started an up-to-date approach to manage DMG, which is adjuvant fractionated external beam radiotherapy along with ONC 201 after tissue diagnosis. Between January 2016 and June 2021, a total of 11 patients with H3 K27M-mutant diffuse midline glioma, diagnosis confirmed by Next-Generation Sequencing (NGS) were enrolled in study. All patients received ONC201 orally once a week following radiotherapy. Safety, and radiological evaluations were regularly assessed every 12 weeks. Among the 11 patients, the median age of diagnosis was 5. Seven (63.6%) patients were male and 4 (36.4%) were female. Primary lesions were localized in the pons in 5 (45.5%) patients, unilateral thalamus (2 on the left, 1 on the right) in 3 (27.3%) patients, bilateral thalamus in 2 (18.2%) patients, and temporo-insular in 1 patient (9.1%). Median progression-free interval was 10 months and median overall survival was 16 months. Diffuse midline glioma has dismal prognosis. None of the treatment options made any dramatic changes in disease course during last 30 years. In our series, diffuse midline glioma patients who had ONC201 tend to have few months more progression free and overall survival (16 vs 11 months) in comparison to patients who had classical treatment in literature. As a neurooncology team, we strongly advocate to obtain tissue samples from diffuse tumors, to establish definite diagnosis and to perform NGS

Dependence Clusters in Alzheimer Disease and Medicare Expenditures: A Longitudinal Analysis From the Predictors Study.

Dependence in Alzheimer disease has been proposed as a holistic, transparent, and meaningful representation of disease severity. Modeling clusters in dependence trajectories can help understand changes in disease course and care cost over time. Sample consisted of 199 initially community-living patients with probable Alzheimer disease recruited from 3 academic medical centers in the United States followed for up to 10 years and had ≥2 Dependence Scale recorded. Nonparametric K-means cluster analysis for longitudinal data (KmL) was used to identify dependence clusters. Medicare expenditures data (1999-2010) were compared between clusters. KmL identified 2 distinct Dependence Scale clusters: (A) high initial dependence, faster decline, and (B) low initial dependence, slower decline. Adjusting for patient characteristics, 6-month Medicare expenditures increased over time with widening between-cluster differences. Dependence captures dementia care costs over time. Better characterization of dependence clusters has significant implications for understanding disease progression, trial design and care planning.

T211. COMPARISON OF REHOSPITALIZATION RATE IN INDIVIDUALS WITH SCHIZOPHRENIA CHANGED FROM PALIPERIDONE PALMITATE TO ORAL ANTIPSYCHOTICS

BackgroundLong-acting antipsychotic therapy (LAT) may help effectively manage individuals with schizophrenia by optimizing adherence, improving treatment response, reducing the risk of relapse, and improving long-term outcomes. LAT has an established role in the maintenance treatment of chronic, poorly adherent, and/or severely ill patients in later stages of schizophrenia.It is not yet known whether the positive effects of these LATs are merely on the control of symptoms and preventing relapse or on changes in insights and attitudes to medications, resulting in changes in disease course.MethodsThis retrospective, single-center study was conducted within the Department of Psychiatry at Inje University Haeundae Paik Hospital. To investigate the efficacy of LAT on the disease course, we compared re-hospitalization rate, drug attitude inventory (DAI), and The Positive and Negative Syndrome Scale (PANSS) in individuals with schizophrenia who had treated with once-monthly paliperidone palmitate and then switched to oral antipsychotics.ResultsA total of 105 patients changed from oral drugs to LAI. Of these, 31 patients were later changed to oral medication.Of the total LAI patients, 32 patients received less than 5 months a week. Thirteen patients were hospitalized for 6 months before LAI change and 3 patients were re-hospitalized during the maintenance period after LAI change. Three patients who did not have hospitalized for 6 months after the change of oral medication but did not have hospitalized during LAI maintenance period were re-hospitalized after changing to oral medication.Of the 72 patients who maintained the LAI for more than 5 months, 28 patients experienced re-hospitalization during oral medication before LAI, 9 of whom were re-hospitalized during the LAI. All of them kept on LAI. Seven patients who changed to oral medication during maintenance were not hospitalized during the maintenance period, but three patients were hospitalized after changing to oral medication. Of the 92 patients who had never been hospitalized within 6 months before the change of LAI, 14 had re-hospitalized after changing to LAI. However, none of the 92 patients who had never been hospitalized changed to oral medication. Regardless of the length of time, 5 (about 16%) were re-hospitalized in 31 patients who changed from LAI to the oral medication again. Interestingly, the patients were not hospitalized during the LAI period.There were 27 dropouts. Twenty patients (19%) after LAI change and 7 patients (6%) after oral change. There was no statistical difference in DAI and PANSS scores after the change from LAI to oral medication.DiscussionAs previously known, the inhibition effect of relapse was evident during the LAI period.There was no change in adherence to medication, attitudes toward treatment, and degree of illness within 6 months. There were 27 dropouts. Twenty patients (19%) after LAI change and seven patients (6%) after oral change. It has been a long time since the onset, and 7 patients have moved to the hospital. Most of these seven patients were considered to be the case of compliance problems. Immediately after the change of oral medication, dropout occurred in 4 patients, and the duration of LAI in these patients was 2–5 months.The lack of statistical difference between DAI and PANSS after changing to oral drug in LAI can be attributed to the short interval of 6 months.

Robust measurement of clinical improvement in patients with cutaneous lupus erythematosus

ObjectiveThe severity and disease course of cutaneous lupus erythematosus (CLE) are highly variable. Consequently, outcome measures for CLE clinical improvement are heterogeneous, complicating treatment decisions and therapeutic development. This study...

Chapter 12 - Neuromuscular disorders in pregnancy

Many neuromuscular disorders preexist or occur during pregnancy. In some cases, pregnancy unmasks a latent hereditary disorder. Most available information is based on case reports or series or retrospective clinical experience or patient surveys. Of special interest are pregnancy-induced changes in disease course or severity and likelihood for baseline recovery of function postpartum. Labor and delivery present special challenges in many conditions that affect skeletal but not smooth (uterine) muscle; so labor complications must be anticipated. Anesthesia for cesarean section surgery requires special precautions in many disorders. The types of conditions reviewed are broad and include examples of autoimmune, hereditary, and compressive/mechanical processes. Disorders include carpal tunnel syndrome and other focal neuropathies, Bell palsy, myasthenia gravis, and other neuromuscular junction disorders, acute and chronic inflammatory neuropathy, hereditary and acquired muscle diseases, spinal muscular atrophy, amyotrophic lateral sclerosis, channelopathies, autonomic neuropathy, and dysautonomia. Many commonly used therapies have fetal animal but no proven human toxicity concerns, complicating treatment and risk decisions. Weaning off effective therapeutic agents or preemptive aggressive treatment or surgery prior to planned pregnancy is an option in some conditions.

Circulating tumour cells mRNA in treatment strategy for melanoma

Abstract Background Circulating tumor cells may reflect the genetic events happening in tumor site what is especially advantageous in case of inability to make biopsy and for monitoring of disease progression and / or treatment effectiveness. Decreasing of distinct mRNA expression levels may indicate positive changes in disease course (for example, decreasing aggressiveness, and risk of metastases). Methods 30 plasma samples of melanoma patients of 3-4 grades and 30 plasma samples of melanoma patients of 2 grade. Specific tailed unidirectional oligonucleotides were designed for 50 genes (selected on the basis of literature data) to perform targeted reverse transcription. Thus, we preserved the quantitative parameters of the chosen genes. Сirculating tumor cells were isolated using OncoQuik kits. Flow cytometry was performed in order to confirm presence of circulating tumor cells. (CD 45-CD146+MUC18+). Sequencing was carried out on a MinIon sequencer. Detected mutations were confirmed by real-time PCR with specific highly sensitive LNA probes. MiRNAs participating in expression regulation of some of the selected genes were assessed in order to monitor epigenetic changes (miRNA-148а-3р, -129-5p, -34a-5p, -363-3p, -374b-5p.) MiRNAs were obtained from circulating tumor cells with miRNeasy Serum/Plasma Advanced Kit. Results 78 mutant sequences were found in the ratio of 0.05% to 45% (mutant fragments compared to wild-type sequences). In 6 samples circulating tumor cells could not be obtained. Detected with MinIon mutations were confirmed with real-time PCR in 8 cases, the differences in the percentage of sequencing results were 30%. In 2 cases, mutations detected during sequencing were not detected using real-time PCR. There was a significant correlation between the severity of the disease and the expression levels of the genes. There was a slight correlation between the miRNA and corresponding mRNA expression levels. Conclusions Identified transcriptome profiles allow to identify targets for specific therapy and/or therapy monitoring, and to identify mutation and epigenetic changes in tumor site. Legal entity responsible for the study The authors. Funding Ministry of Science and Higher Education of the Russian Federation Project 5-100. Disclosure All authors have declared no conflicts of interest.

Clinical Decision Support System: A Pragmatic Tool to Improve Acute Exacerbation of COPD Discharge Recommendations

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with significant mortality, morbidity and increased risk for further exacerbations. Therefore, appropriate measures for prevention of further exacerbations should be initiated before discharge. Unfortunately, this opportunity for treatment review and change in disease course is often missed. We designed a decision support tool to automatically generate discharge recommendations for COPD patients based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report. A pre- and post-intervention study was conducted including data from 24 months before and 18 months after the implementation of the tool. The rate of adherence of the discharge recommendations to the report was measured. Overall, 536 patients were included in the pre-intervention cohort and 367 in the intervention cohort. Demographic and clinical features were similar between the two groups. After introduction of the tool, the percentage of patients discharged with long-acting medications increased from 42% to 84%, recommendations for smoking cessation increased from 32% to 91%, for vaccination from 13% to 92%, and for follow-up visit in a pulmonology clinic from 72% to 98%. Of the patients given prescriptions for long-acting bronchodilators, 54% purchased these after discharge versus 20% of the patients without such prescriptions. Decision-support tools can significantly improve adherence to guidelines among patients discharged after hospitalization due to Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) and potentially improve their clinical course.

Pathomorphosis of idiopathic generalized epilepsies

To study the pathomorphosis of idiopathic generalized epilepsies (IGE) in a large population of adult patients with long-term follow-up. The study involved 1480 patients with epilepsy, including 281 patients with IGE. In 26 patients with childhood absence epilepsy (CAE), age-related changes in disease course have been particularly pronounced. None of the patients had frequent typical absences ('pyknolepsy') at the time of the survey. Sixteen of 26 patients had predominantly rare generalized tonic-clonic seizures in combination with occasional absences or myoclonic jerks, while in 2 patients there was the transition from the DAE to juvenile myoclonic epilepsy (JME). The EEG recorded in the 'adult' age showed the level of epileptiform activity in only 12 patients out of 26 (in 2 patients only during nighttime video-EEG-monitoring). EEG changes resembled a 'juvenile' form of epilepsy. At the time of completion of the study, 13 patients were free of seizures and only 5 of 26 patients with DAE did not require treatment with antiepileptic drugs. In patients with Jeavons (n=14) and Tassinari (n=1) syndromes, the disease did not change over time. The pathomorphosis of IGE with childhood onset depends on the certain epileptic syndrome.

Chapter 17 - New symptomatic therapies for Huntington disease

Huntington disease (HD), an inherited neurodegenerative disease, results from a CAG repeat expansion creating mutant huntingtin protein and widespread neuronal damage. Motor symptoms such as chorea are often preceded by cognitive and behavioral changes. Tetrabenazine and deutetrabebenazine are the two drugs approved by the Federal Food and Drug Administrationfor HD symptoms, is an effective therapy for chorea. However, there is still a large need for other symptomatic therapies impacting functional issues, including impaired gait, behavioral, and cognitive symptoms. A number of pharmacologic agents are under investigation. Additionally, other mechanisms are being targeted in motor symptom drug development, including phosphodiesterase 10 enzyme inhibition, dopamine modulation, and inhibition of deacetylation. There is perhaps the greatest unmet need in treating nonmotor effects, such as cognition and change in disease course. PBT2, a metal chaperone, and latrepirdine, a mitochondrial stabilizer, are under investigation specifically for the possibility of cognitive benefit. Unfortunately, there is a lack of HD-specific evidence on effective treatments for behavioral and psychiatric symptoms. Further investigation of nonmedication interventions such as physical therapy is necessary. As our understanding of molecular and cellular mechanisms underlying HD broadens, a new set of mechanistic targets will become the focus of HD symptomatic therapies.

Follow-up of patients with functional bowel symptoms treated with a low FODMAP diet.

To investigate patient-reported outcomes from, and adherence to, a low FODMAP diet among patients suffering from irritable bowel syndrome and inflammatory bowel disease. Consecutive patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) and co-existing IBS fulfilling the ROME III criteria, who previously attended an outpatient clinic for low FODMAP diet (LFD) dietary management and assessment by a gastroenterologist, were invited to participate in a retrospective questionnaire analysis. The questionnaires were sent and returned by regular mail and gathered information on recall of dietary treatment, efficacy, symptoms, adherence, satisfaction, change in disease course and stool type, and quality of life. Before study enrolment all patients had to sign an informed written consent. One hundred and eighty patients were included, 131 (73%) IBS and 49 (27%) IBD patients. Median age was 43 years (range: 18-85) and 147 (82%) were females. Median follow-up time was 16 mo (range: 2-80). Eighty-six percent reported either partial (54%) or full (32%) efficacy with greatest improvement of bloating (82%) and abdominal pain (71%). The proportion of patients with full efficacy tended to be greater in the IBD group than in the IBS group (42% vs 29%, P = 0.08). There was a significant reduction in patients with a chronic continuous disease course in both the IBS group (25%, P < 0.001) and IBD group (23%, P = 0.002) along with a significant increase in patients with a mild indolent disease course of 37% (P < 0.001) and 23% (P = 0.002), respectively. The proportion of patients having normal stools increased with 41% in the IBS group (P < 0.001) and 66% in the IBD group (P < 0.001). One-third of patients adhered to the diet and high adherence was associated with longer duration of dietary course (P < 0.001). Satisfaction with dietary management was seen in 83 (70%) IBS patients and 24 (55%) IBD patients. Eighty-four percent of patients lived on a modified LFD, where some foods rich in FODMAPs were reintroduced, and 16% followed the LFD by the book without deviations. Wheat, dairy products, and onions were the foods most often not reintroduced by patients. These data suggest that a diet low in FODMAPs is an efficacious treatment solution in the management of functional bowel symptoms for IBS and IBD patients.

FRI0140 Developing Quality Criteria from the Assessments in Ankylosing Spondylitis Society (ASAS) and European League against Rheumatism (EULAR) Ankylosing Spondylitis Management Recommendations: towards Quantitative Definitions of “Non-Compliance”

BackgroundIn 2010, the Assessments in Ankylosing Spondylitis Society (ASAS) and the European League Against Rheumatism (EULAR) updated management recommendations for ankylosing spondylitis. Applicable to all patients with axial spondyloarthritis (SpA),...

Fecal Microbial Composition of Ulcerative Colitis and Crohn’s Disease Patients in Remission and Subsequent Exacerbation

BackgroundLimited studies have examined the intestinal microbiota composition in relation to changes in disease course of IBD over time. We aimed to study prospectively the fecal microbiota in IBD patients developing an exacerbation during follow-up.DesignFecal samples from 10 Crohn’s disease (CD) and 9 ulcerative colitis (UC) patients during remission and subsequent exacerbation were included. Active disease was determined by colonoscopy and/or fecal calprotectine levels. Exclusion criteria were pregnancy, antibiotic use, enema use and/or medication changes between consecutive samples. The microbial composition was assessed by 16S rDNA pyrosequencing.ResultsAfter quality control, 6,194–11,030 sequences per sample were available for analysis. Patient-specific shifts in bacterial composition and diversity were observed during exacerbation compared to remission, but overarching shifts within UC or CD were not observed. Changes in the bacterial community composition between remission and exacerbation as assessed by Bray-Curtis dissimilarity, were significantly larger in CD versus UC patients (0.59 vs. 0.42, respectively; p = 0.025). Thiopurine use was found to be a significant cause of clustering as shown by Principal Coordinate Analysis and was associated with decreases in bacterial richness (Choa1 501.2 vs. 847.6 in non-users; p<0.001) and diversity (Shannon index: 5.13 vs. 6.78, respectively; p<0.01).ConclusionShifts in microbial composition in IBD patients with changing disease activity over time seem to be patient-specific, and are more pronounced in CD than in UC patients. Furthermore, thiopurine use was found to be associated with the microbial composition and diversity, and should be considered when studying the intestinal microbiota in relation to disease course.

Detecting Changes in Retinal Function: Analysis with Non-Stationary Weibull Error Regression and Spatial Enhancement (ANSWERS)

Visual fields measured with standard automated perimetry are a benchmark test for determining retinal function in ocular pathologies such as glaucoma. Their monitoring over time is crucial in detecting change in disease course and, therefore, in prompting clinical intervention and defining endpoints in clinical trials of new therapies. However, conventional change detection methods do not take into account non-stationary measurement variability or spatial correlation present in these measures. An inferential statistical model, denoted ‘Analysis with Non-Stationary Weibull Error Regression and Spatial enhancement’ (ANSWERS), was proposed. In contrast to commonly used ordinary linear regression models, which assume normally distributed errors, ANSWERS incorporates non-stationary variability modelled as a mixture of Weibull distributions. Spatial correlation of measurements was also included into the model using a Bayesian framework. It was evaluated using a large dataset of visual field measurements acquired from electronic health records, and was compared with other widely used methods for detecting deterioration in retinal function. ANSWERS was able to detect deterioration significantly earlier than conventional methods, at matched false positive rates. Statistical sensitivity in detecting deterioration was also significantly better, especially in short time series. Furthermore, the spatial correlation utilised in ANSWERS was shown to improve the ability to detect deterioration, compared to equivalent models without spatial correlation, especially in short follow-up series. ANSWERS is a new efficient method for detecting changes in retinal function. It allows for better detection of change, more efficient endpoints and can potentially shorten the time in clinical trials for new therapies.