Ponatinib vs. Imatinib as Frontline Treatment for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Matching Adjusted Indirect Comparison.

INTRODUCTION: Efficacy of ponatinib-based treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) has not been compared to imatinib-based treatments in head-to-head clinical trials. We evaluated its efficacy versus imatinib-based regimens using a matching adjusted indirect comparison. METHODS: Two ponatinib studies were used: the phase 2 MDACC study of ponatinib + hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) in adult patients and the phase 2 GIMEMA LAL1811 study of ponatinib + steroids in patients > 60 years/unfit for intensive chemotherapy and stem cell transplant. Studies on imatinib as first-line treatment in adults with Ph + ALL were identified using a systematic literature search. Population adjustment was based on the prognostic factors and effect modifiers identified by clinical experts. Hazard ratios (HRs) were calculated for overall survival (OS) and odds ratios (ORs) for complete molecular response (CMR). RESULTS: The systematic literature search identified two studies (GRAAPH-2005 and NCT00038610) reporting the efficacy of first-line imatinib + hyper-CVAD and one study reporting the efficacy of first-line imatinib monotherapy induction + imatinib-based consolidation (CSI57ADE10). Ponatinib + hyper-CVAD prolonged OS and gave a higher CMR rate than imatinib + hyper-CVAD. The adjusted HR [95% confidence interval (CI)] for OS was 0.35 (0.17-0.74) for MDACC vs. GRAAPH-2005 and 0.35 (0.18-0.70) for MDACC vs. NCT00038610; the adjusted OR (95% CI) for CMR was 12.11 (3.77-38.87) for MDACC vs. GRAAPH-2005 and 5.65 (2.02-15.76) for MDACC vs. NCT00038610. Ponatinib + steroids prolonged OS and gave a higher CMR rate than imatinib monotherapy induction + imatinib-containing consolidation. The adjusted HR (95% CI) for OS was 0.24 (0.09-0.64) and the adjusted OR (95% CI) for CMR was 6.20 (1.60-24.00) for GIMEMA LAL1811 vs. CSI57ADE10. CONCLUSION: In adults with newly diagnosed Ph + ALL, first-line treatment with ponatinib was associated with better outcomes than first-line treatment with imatinib.

Impact of COVID-19 on ischemic stroke care in Hungary.

Data about the coronavirus disease 2019 (COVID-19) pandemic's collateral damage on ischemic stroke (IS) care during the second epidemic wave in Central Europe are limited. We sought to evaluate the impact of the COVID-19 outbreak on Hungarian IS care during the two epidemic waves. This retrospective observational study was based on a nationwide reimbursement database that encompasses all IS admissions and all reperfusion interventions, i.e., intravenous thrombolysis (IVT) and endovascular therapy (EVT) from 2 January 2017 to 31 December 2020 in Hungary. COVID-19 pandemic's effect on the number of IS admissions and reperfusion interventions were analyzed using different statistics: means, medians, trends, relative rates, and linear relationships. The mean and median values of IS admissions and reperfusion interventions decreased only in some measure during the COVID-periods. However, trend analysis demonstrated a significant decline from the trends. The decline's dynamic and amplitude have differed for each variable. In contrast to IVT, the number of IS admissions and EVTs negatively correlated with the epidemic waves' amplitude. Besides, the decrease in the number of IS admissions was more pronounced than the decrease in the number of reperfusion interventions. Our study demonstrated a significant disruption in IS care during the COVID-19 epidemic in Hungary, in which multiple different factors might play a role. The disproportionate reduction of IS admission numbers could partially be explained by the effect of health emergency operative measures and changes in patients' social behavior. Further studies are needed to evaluate the causes of our observations.

Age and gender characteristics of patients affected with multiple sclerosis in Hungary between 2004 and 2016 / A hazai sclerosis multiplex betegpopuláció életkori és nemi megoszlása 2004 és 2016 között.

Összefoglaló. Bevezetés: Mivel hazánkban a sclerosis multiplex gyakoriságáról, valamint életkori és nemi jellegzetességeirol az elmúlt évtizedekben - egészen 2020-ig - csak regionális jellegu felmérések készültek egy-egy centrum betegforgalma alapján, az újonnan diagnosztizált és már ismert betegek országos koreloszlásáról és annak idobeli változásairól nincsenek ismereteink. Célkituzés: Jelen munkánkban több mint 14 000 beteg adatainak elemzésével a prevalens és incidens betegek koreloszlásának változását vizsgáljuk 2004-2016 során, és eredményeinket összevetjük az elmúlt évtizedekben közölt hazai adatokkal. Módszer: Munkacsoportunk az egészségbiztosítási pénztár anonimizált NEUROHUN adatbázisát elemezte, amely tartalmazza a 2004 és 2016 között az összes hazai, államilag finanszírozott, a fekvo- és járóbeteg-szakellátásból neurológiai diagnózissal jelentett esetet. A sclerosis multiplex BNO-kódjának elofordulása alapján korábban létrehoztuk a betegség adminisztratív definícióját, és megbecsültük a sclerosis multiplex országos prevalenciáját és incidenciáját. Eredmények: A prevalens betegek átlagéletkora 2015-ben 47,9 év, ugyanebben az évben az incidens betegek átlagéletkora 37,4 év volt. Vizsgálatunk szerint a prevalens betegek átlagéletkora szignifikánsan - évente egyötöd-egyharmad évvel (p<0,001) - emelkedik, mégpedig a nok esetében nagyobb mértékben. A nok átlagosan fél évvel idosebbek, mint a férfi páciensek (szignifikáns különbség: p = 0,002). A prevalens betegekben a legnépesebb korosztály az ötvenévesek felol a fiatalabb, 35-40 éves korosztály felé mozdul. Az incidens betegek átlagéletkora lassan, de szignifikánsan - évente átlagosan egyharmad évvel (p<0,001) - csökken. Következtetés: Eredményeink szerint az újonnan diagnosztizált sclerosis multiplexes páciensek átlagosan egyre fiatalabbak, és a prevalens betegek között is egyre fiatalabb korosztályok a legnépesebbek, de a javuló túlélés és a hosszabb élettartam miatt a prevalens betegek átlagéletkora összességében valószínuleg fokozatosan emelkedik. Orv Hetil. 2021; 162(19): 746-753. INTRODUCTION: The nationwide age and gender distribution of newly diagnosed and prevalent multiple sclerosis patients has been unknown in Hungary, as until 2020 only regional studies had been reported about the frequency and age characteristics of subjects with multiple sclerosis, based on single-center patient registries. OBJECTIVE: In the present study with the analysis of over 14 000 patients, we describe the changes in age distribution of prevalent and incident subjects between 2004 and 2016 and compare our results with the data published on the subject during the last decades in Hungary. METHOD: We have analyzed the pseudonymized NEUROHUN database provided by the single-payer National Health Insurance Fund, that contains each claim submitted by public hospitals and outpatient services for neurologic diseases between 2004 and 2016. Using the ICD10-code of multiple sclerosis, we have previously established the administrative definition of the illness and estimated its prevalence and incidence in the country. RESULTS: The mean age of prevalent patients was 47.9 years in 2015, whereas in the same year the mean age of incident cases was 37.4 years. The average age of prevalent patients shows a significant rise - with an annual increase of one fifth-one third year (p<0.001) - with a more pronounced increase among women. The age of women is higher by half a year (p = 0.002). The most populous age groups among prevalent subjects shift from the fifties towards the younger generations between 35-40 years of age. The average age of incident subjects slowly, but significantly decreases, with a mean annual decrease of about one third year (p<0.001). CONCLUSION: Our results suggest that though new patients are younger year-by-year and the most populous age groups are also younger, altogether the average age of prevalent subjects continuously increases, probably due to the longer survival and lifespan of patients with multiple sclerosis. Orv Hetil. 2021; 162(19): 746-753.

Socioeconomic Factors Predicting Depression Differ in the Acute Stage and at 1 year After Ischemic Stroke or TIA.

INTRODUCTION: Considerable depressive symptoms follow stroke in about one third of patients. Initial depressive symptoms may wane after the acute phase of stroke, but persisting depressive symptoms adversely affect rehabilitation and quality of life. We set forth to evaluate predictors of depressive symptoms with a focus on socioeconomic factors. METHODS: We evaluated clinical features and socioeconomic characteristics in 233 consecutive patients with acute ischemic stroke or TIA. Depressive symptoms could be evaluated in 168 subjects in the acute phase with a repeated testing after a mean of 14.7 months via telephone interview in 116 patients. Survival status, scores on the Center for Epidemiologic Studies-Depression Scale (CES-D), Beck Depression Inventory (BDI) and disability (modified Rankin scale, mRS) were recorded. RESULTS: In the acute phase, employment status (p = 0.037) and level of education (p = 0.048) whereas one year later dependency (mRS≥3, p = 0.002) and income (p = 0.012) were the significant predictors of the severity of depressive symptoms. A change from independent (mRS≤2) to dependent living predicted worsening depressive symptoms (p = 0.008), whereas improving to functional independence from an initially dependent condition was associated with diminishing depressive symptoms (p = 0.077 for CES-D and p = 0.044 for BDI) in the first year after an acute ischemic cerebrovascular event. CONCLUSIONS: Predictors of the severity of depressive symptoms differed in the acute phase and at follow-up. In addition to disability, education and employment status in the acute phase and income in the late phase predict the severity of depressive symptoms after ischemic stroke or TIA.

Health related quality of life and satisfaction with care of stroke patients in Budapest: A substudy of the EuroHOPE project.

BACKGROUND: Disadvantaged socioeconomic status is associated with higher stroke incidence and mortality, and higher readmission rate. We aimed to assess the effect of socioeconomic factors on case fatality, health related quality of life (HRQoL), and satisfaction with care of stroke survivors in the framework of the European Health Care Outcomes, Performance and Efficiency (EuroHOPE) study in Hungary, one of the leading countries regarding stroke mortality. METHODS: We evaluated 200 consecutive patients admitted for first-ever ischemic stroke in a single center and performed a follow-up at 3 months after stroke. We recorded pre- and post-stroke socioeconomic factors, and assessed case fatality, HRQoL and patient satisfaction with the care received. Stroke severity at onset was scored by the National Institutes of Health Stroke scale (NIHSS), disability at discharge from acute care was evaluated by the modified Rankin Score (mRS). To evaluate HRQoL and patient satisfaction with care we used the EQ-5D-5L, 15D and EORTC IN PATSAT 32 questionnaires. RESULTS: At 3 months after stroke the odds of death was significantly increased by stroke severity (NIHSS, OR = 1.209, 95%CI: 1.125-1.299, p<0.001) and age (OR = 1.045, 95%CI: 1.003-1.089, p = 0.038). In a multiple linear regression model, independent predictors of HRQoL were age, disability at discharge, satisfaction with care, type of social dwelling after stroke, length of acute hospital stay and rehospitalization. Satisfaction with care was influenced negatively by stroke severity (Coef. = -1.111, 95%C.I.: -2.159- -0.062, p = 0.040), and positively by having had thrombolysis (Coef. = 25.635, 95%C.I.: 5.212-46.058, p = 0.016) and better HRQoL (Coef. = 22.858, 95%C.I.: 6.007-39.708, p = 0.009). CONCLUSION: In addition to age, disability, and satisfaction with care, length of hospital stay and type of social dwelling after stroke also predicted HRQoL. Long-term outcome after stroke could be improved by reducing time spent in hospital, i.e. by developing home care rehabilitation facilities thus reducing the need for readmission to inpatient care.

The prevalence of psychiatric symptoms before the diagnosis of Parkinson's disease in a nationwide cohort: A comparison to patients with cerebral infarction.

OBJECTIVES: Psychiatric symptoms (PS) can be non-motor features in Parkinson's disease (PD) which are common even in the prodromal, untreated phase of the disease. Some PS, especially depression and anxiety recently became known predictive markers for PD. Our objective was to explore retrospectively the prevalence of PS before the diagnosis of PD. METHODS: In the framework of the Hungarian Brain Research Program we created a database from medical and medication reports submitted for reimbursement purposes to the National Health Insurance Fund in Hungary, a country with 10 million inhabitants and a single payer health insurance system. We used record linkage to evaluate the prevalence of PS before the diagnosis of PD and compared that with patients with ischemic cerebrovascular lesion (ICL) in the period between 2004-2016 using ICD-10 codes of G20 for PD, I63-64 for ICL and F00-F99 for PS. We included only those patients who got their PD, ICL and psychiatric diagnosis at least twice. RESULTS: There were 79 795 patients with PD and 676 874 patients with ICL. Of the PD patients 16% whereas of those with ischemic cerebrovascular lesion 9.7% had a psychiatric diagnosis before the first appearance of PD or ICL (p<0.001) established in psychiatric care at least twice. The higher rate of PS in PD compared to ICL remained significant after controlling for age and gender in logistic regression analysis. The difference between PD and ICL was significant for Mood disorders (F30-F39), Organic, including symptomatic, mental disorders (F00-F09), Neurotic, stress-related and somatoform disorders (F40-F48) and Schizophrenia, schizotypal and delusional disorders (F20-F29) diagnosis categories (p<0.001, for all). DISCUSSION: The higher rate of psychiatric morbidity in the premotor phase of PD may reflect neurotransmitter changes in the early phase of PD.

Incidence and prevalence of multiple sclerosis in Hungary based on record linkage of nationwide multiple healthcare administrative data.

OBJECTIVES: As there were only regional studies in Hungary about the prevalence of multiple sclerosis (MS), we aimed to estimate its epidemiological features using data of Hungary's single-payer health insurance system. METHODS: Pseudonymized database of claims reported by hospitals and outpatient services between 2004-2016 was analyzed and linked with an independent database of outpatient pharmacy refills between 2010-2016. We established an administrative case definition of MS and validated it on medical records of 309 consecutive patients. A subject was defined as MS-patient if received MS diagnosis (International Classification of Diseases, 10th edition, code G35) on three or more occasions at least in 2 calendar years and at least once documented by a neurologist. Patients were counted as incident cases in the year of the first submitted claim for MS. We allowed a 6-year-long run-in period, so only data between 2010-2015 are discussed. RESULTS: Sensitivity of the administrative case definition turned out to be 99%, while specificity was >99%. Crude prevalence of MS has increased from 109.3/100,000 in 2010 to 130.8/100,000 in 2015 (p-value = 0.000003). Crude incidence declined from 7.1/100,000 (2010) to 5.4/100,000 (2015) (p-value = 0.018). Direct standardization - based on European standard population and results of nationwide Hungarian census of 2011 - revealed that age standardized prevalence was 105.2/100,000 (2010), which has grown to 127.2/100,000 (2015) (p-value = 0.000001). Age standardized incidence rate declined from 6.7/100,000 (2010) to 5.1/100,000 (2015) (p-value = 0.016). The ratio of MS-patients receiving ≥1 prescription for disease modifying treatment increased from 0.19 (2010) to 0.29 (2015) (p-value = 0.0051). The female/male ratio of prevalent cases remained 2.6. DISCUSSION: The prevalence of MS in Hungary is higher than previously reported, the incidence rate is moderate. The prevalence is rising, the incidence rate shows decline. The proportion of patients receiving disease modifying treatment grows but was still around 30% in 2015.

Notification Strategy and Predictors of Outcome in Stroke Ineligible for Reperfusion Therapies.

Background, Objective: At least 70% of all stroke patients are ineligible for recanalization therapy. We identified predictors of outcome among these patients, with special focus on notification of emergency medical services (EMS). Methods: We prospectively collected data of 250 consecutive patients with acute cerebrovascular diseases ineligible for recanalization therapy. Initial notification strategy and outcome were analyzed by regression models. Results: EMS notification rate was 55, 41, and 21% in patients with <6, 6-24, and >24 h stroke-to-door time. Atrial fibrillation (AF; OR = 2.66, 95% CI: 1.19-5.96), stroke severity (National Institutes of Health Stroke Scale score, NIHSS; OR = 1.12, 95% CI: 1.02-1.23), history of any psychiatric disease (OR = 2.2, 95% CI: 0.98-4.97), aphasia (OR = 1.99, 95% CI: 0.99-3.98), and residence type were predictors of EMS notification. Disability (modified Rankin Scale score [mRS]) both at discharge and at 1 year was associated with age, admission NIHSS score, type of cerebrovascular disorder, and pre-stroke mRS at discharge and discharge mRS at follow-up. Age (HR = 1.05, 95% CI: 1.02-1.08) and NIHSS (HR = 1.16, 95% CI: 1.12-1.21) had a significant effect on the relative hazard of death. Conclusions: EMS notification is influenced by AF, stroke severity, psychiatric disease, aphasia, and residence type. Early disability depends on age, the type and severity of the stroke, and pre-stroke mRS. Predictors of disability at 1 year after stroke are age, stoke severity, mRS at discharge, and recurrent ischemic stroke. Higher NIHSS and older age are associated with higher case fatality. In patients ineligible for recanalization, EMS notification had no significant effect on outcome, regarding both disability and survival.