Long-term real-world effectiveness and safety of fingolimod over 5 years in Germany

Objective To evaluate the 5-year real-world benefit–risk profile of fingolimod in patients with relapsing–remitting MS (RRMS) in Germany. Methods Post-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA) is a non-interventional real-world study to prospectively assess the effectiveness and safety of fingolimod in routine clinical practice in Germany. The follow-up period comprised 5 years. Patients were included if they had been diagnosed with RRMS and had been prescribed fingolimod as part of clinical routine. There were no exclusion criteria except the contraindications for fingolimod as defined in the European label. The effectiveness and safety analysis set comprised 4032 and 4067 RRMS patients, respectively. Results At the time of the 5-year follow-up of PANGAEA, 66.57% of patients still continued fingolimod therapy. Annualized relapse rates decreased from baseline 1.5 ± 1.15 to 0.42 ± 0.734 at year 1 and 0.21 ± 0.483 at year 5, and the disability status remained stable, as demonstrated by the Expanded Disability Status Scale mean change from baseline (0.1 ± 2.51), the decrease of the Multiple Sclerosis Severity Score from 5.1 ± 2.59 at baseline to 3.9 ± 2.31 at the 60-months follow-up, and the percentage of patients with ‘no change’ in the Clinical Global Impression scale at the 60-months follow-up (78.11%). Adverse events (AE) occurring in 75.04% of patients were in line with the known safety profile of fingolimod and were mostly non-serious AE (33.62%) and non-serious adverse drug reactions (50.59%; serious AE 4.98%; serious ADR 10.82%). Conclusions PANGAEA demonstrated the sustained beneficial effectiveness and safety of fingolimod in the long-term real-world treatment of patients with RRMS.

Management of patients with herpes-associated recurrent vulvovaginal candidiasis

Objective. To develop a diagnostic algorithm, a rational method of treatment, and principles of preconception care in women with herpes-associated recurrent vulvovaginal candidiasis (RVVC).Materials and methods. We examined 68 patients with herpes-associated RVVC and 20 gynecologically healthy women.Results. It has been found that in RVVC it is necessary to study vaginal swab culture with the determination of the microorganism and its biofilm-forming ability in combination with viral DNA detection by the polymerase chain reaction (PCR) in vaginal secretion, determination of the IgG titer to the herpes simplex virus (HSV), the avidity index to HSV I and II. In the presence of laboratory-confirmed RVVC and HSV infection, it is necessary to assume the presence of an atypical course of HSV infection followed by complex antiviral and antimycotic therapy.Conclusion. The use of the developed algorithm of diagnostic and treatment interventions as preconception care makes it possible to address symptoms, reduce relapse rates and extend a non-relapse interval, prepare women with the mixed-infection for favorable pregnancy outcomes.

A Cross-Sectional, Questionnaire-Based Study on Drug Treatment Awareness in Schizophrenia Patients and Caregivers: An Unexplored Avenue

Background: Schizophrenia is associated with high relapse rates, and medication nonadherence is a major factor contributing toward relapse. Since medication adherence and treatment awareness are linked, an alarming need was felt to evaluate the level of drug treatment awareness in patients who have schizophrenia. Besides, patients who have schizophrenia are often dependent on their caregivers for medications. Hence, the current study was also designed to look into drug treatment awareness among caregivers. Methods: This was a cross-sectional, questionnaire-based study. Patients diagnosed with schizophrenia as per The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition were included, provided they had good insight and had been prescribed medications at the study center for at least three months. Caregivers were included using the Pollak and Perlick criteria. The sociodemographic profile of the patients and caregivers was recorded, and further assessment for treatment awareness was done using the prevalidated Drug Treatment Awareness Questionnaire (DTAQ). Results: A total of 166 patients and 157 caregivers were enrolled. Mean drug awareness scores among patients and caregivers did not show statistically significant differences (P= 0.22). Mean ± SD DTAQ awareness scores in patients and caregivers were 12.57 ± 1.81 and 12.84 ± 1.91, respectively. The majority of patients and caregivers (> 90%) possessed awareness in domains related to past medication records and in that of re-visit/re-contact instructions. Awareness was least commonly seen in relation to side effects of medications and details of the prescribed medications, where only about 50% of patients and caregivers possessed awareness. No clinically significant correlation was found between sociodemographic factors and drug treatment awareness scores. Conclusion: Drug treatment awareness in patients and caregivers was comparable and was not reliant on the sociodemographic factors. Special interventions should be conducted to raise drug treatment awareness among patients having insight and their caregivers.

Relapse activity in the chronic phase of anti-myelin-oligodendrocyte glycoprotein antibody-associated disease

Objective The patterns of relapse and relapse-prevention strategies for anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not completely investigated. We compared the patterns of relapse in later stages of MOGAD with those of anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD). Methods In this observational, comparative cohort study, 66 patients with MOGAD and 90 with AQP4-Ab-positive NMOSD were enrolled. We compared the patterns of relapse and annualized relapse rates (ARRs) in the first 10 years from disease onset, stratified by relapse-prevention treatments. Results Approximately 50% of the patients with MOGAD experienced relapses in the first 10 years. Among those not undergoing relapse-prevention treatments, ARRs in the first 5 years were slightly lower in MOGAD patients than in AQP4-Ab-positive NMOSD patients (MOGAD vs. AQP4-Ab NMOSD: 0.19 vs. 0.30; p = 0.0753). After 5 years, the ARR decreased in MOGAD patients (MOGAD vs. AQP4-Ab NMOSD: 0.05 vs. 0.34; p = 0.0001), with a 72% reduction from the first 5 years (p = 0.0090). Eight (61.5%) of the 13 MOGAD patients with more than 10-year follow-up from disease onset showed relapse 10 years after onset. Clustering in the timing and phenotype of attacks was observed in both disease patients. The effectiveness of long-term low-dose oral PSL for relapse prevention in patients with MOGAD has not been determined. Conclusions The relapse risk in patients with MOGAD is generally lower than that in patients with AQP4-Ab-positive NMOSD, especially 5 years after onset. Meanwhile, relapses later than 10 years from onset are not rare in both diseases.

Inpatient Mental Healthcare before and during the COVID-19 Pandemic

Prior studies have demonstrated disruption to outpatient mental health services after the onset of the COVID-19 pandemic. Inpatient mental health services have received less attention. The current study utilized an existing cohort of 33 Veterans Health Affairs (VHA) acute inpatient mental health units to examine disruptions to inpatient services. It further explored the association between patient demographic, clinical, and services variables on relapse rates. Inpatient admissions and therapeutic services (group and individual therapy and peer support) were lower amongst the COVID-19 sample than prior to the onset of COVID-19 while lengths of stay were longer. Relapse rates did not differ between cohorts. Patients with prior emergent services use as well as substance abuse or personality disorder diagnoses were at higher risk for relapse. Receiving group therapy while admitted was associated with lower risk of relapse. Inpatient mental health services saw substantial disruptions across the cohort. Inpatient mental health services, including group therapy, may be an important tool to prevent subsequent relapse.

Tisagenlecleucel Outcomes in Relapsed/Refractory Extramedullary ALL: A Pediatric Real World CAR Consortium Report.

Chimeric antigen receptor (CAR) T-cells have transformed the therapeutic options for relapsed/refractory (R/R) B-cell ALL. Data for CAR therapy in extramedullary (EM) involvement is limited. Retrospective data was abstracted from the Pediatric Real World CAR Consortium (PRWCC) of 184 infused patients from 15 US institutions. Response (CR) rate, overall survival (OS), relapse-free survival (RFS), and duration of B-cell aplasia (BCA) in patients referred for tisagenlecleucel with EM disease (both CNS3 and non-CNS EM) were compared to bone marrow (BM) only. Patients with CNS disease were further stratified for comparison. Outcomes are reported on 55 patients with EM disease prior to CAR (n=40 CNS3; n=15 non-CNS EM). The median age at infusion in CNS cohort was 10 years (range <1-25) and the non-CNS EM cohort was 13 years (2-26). In patients with CNS disease, 88% (35/40) achieved a CR, versus only 66% (10/15) with non-CNS EM disease. Patients with CNS disease (both with and without marrow involvement) had comparable 24-month OS outcomes to non-CNS EM or BM only (p=0.41). There was no difference in 12-month RFS between CNS, non-CNS EM, or BM only patients (p=0.92). No increased toxicity was seen with CNS or non-CNS EM disease (p=0.3). Active CNS disease at time of infusion did not impact outcomes. Isolated (iCNS) disease trended towards improved OS when compared to combined CNS and BM (p=0.12). R/R EM disease can be effectively treated with tisagenlecleucel with toxicity, relapse rates and survival rates comparable to patients with BM only. Outcomes for iCNS relapse are encouraging.

Outcomes of women treated with progestin and metformin for atypical endometrial hyperplasia and early endometrial cancer: a systematic review and meta-analysis

ObjectiveProgestin therapy is the recommended fertility-sparing management of atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. Our objective was to evaluate disease relapse after progestin and metformin versus progestin therapy alone in patients with endometrial hyperplasia or cancer. Our secondary outcomes were disease remission, clinical pregnancy and live birth rate.MethodsA systematic review of the literature was conducted (MEDLINE, Web of Science, Cochrane Library, CINAHL, LILACS, clinicaltrials.gov) from inception to April 2021. Studies of reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer who received progestin and metformin or progestin alone for fertility-sparing management, were included in the review. Early endometrial cancer was defined as grade 1, stage 1 disease. Exclusion criteria included women with higher grade endometrial cancer and when conservative management was not for fertility-sparing purposes. Data are presented as odds ratios (ORs) and 95% confidence intervals (CIs) with fixed or random effects meta-analysis. Quality scoring was based on the Newcastle-Ottawa and Jadad scales.ResultsIn total, 271 reports were identified and six studies met the inclusion criteria. These studies included 621 women; 241 (38.8%) patients received combined therapy and 380 (61.2%) received progestin therapy alone. Relapse rates were lower for progestin and metformin than for progestin therapy alone (pooled OR 0.46, 95% CI 0.24 to 0.91, p=0.03). The remission rates were not different (pooled OR 1.35, 95% CI 0.91 to 2.00, p=0.14). Women who received progestin and metformin achieved pregnancy and live birth rates similar to those who received progestin therapy only (pooled OR 1.01, 95% CI 0.44 to 2.35, p=0.98; pooled OR 0.46, 95% CI 0.21 to 1.03, p=0.06).ConclusionFor reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer, progestin and metformin therapy compared with progestin therapy alone is associated with lower relapse rates, and similar remission, clinical pregnancy and live birth rates.PROSPERO registration numberCRD42020179069.disease remission,

Chlorine, chromium, proteins of oxidative stress and DNA repair pathways are related to prognosis in oral cancer

The comparison of chemical and histopathological data obtained from the analysis of excised tumor fragments oral squamous cell carcinoma (OSCC) with the demographic and clinical evolution data is an effective strategy scarcely explored in OSCC studies. The aim was to analyze OSCC tissues for protein expression of enzymes related to oxidative stress and DNA repair and trace elements as candidates as markers of tumor aggressiveness and prognosis. Tumor fragments from 78 OSCC patients that had undergone ablative surgery were qualitatively analyzed by synchrotron micro-X-ray fluorescence for trace elements. Protein expression of SOD-1, Trx, Ref-1 and OGG1/2 was performed by immunohistochemistry. Sociodemographic, clinical, and histopathological data were obtained from 4-year follow-up records. Disease relapse was highest in patients with the presence of chlorine and chromium and lowest in those with tumors with high OGG1/2 expression. High expression of SOD-1, Trx, and Ref-1 was determinant of the larger tumor. Presence of trace elements can be markers of disease prognosis. High expression of enzymes related to oxidative stress or to DNA repair can be either harmful by stimulating tumor growth or beneficial by diminishing relapse rates. Interference on these players may bring novel strategies for the therapeutic management of OSCC patients.

Smoking Cessation Apps: A Systematic Review of Format, Outcomes, and Features

Smoking cessation interventions are effective, but they are not easily accessible for all treatment-seeking smokers. Mobile health (mHealth) apps have been used in recent years to overcome some of these limitations. Smoking cessation apps can be used in combination with a face-to-face intervention (FFSC-Apps), or alone as general apps (GSC-Apps). The aims of this review were (1) to examine the effects of FFSC-Apps and GSC-Apps on abstinence, tobacco use, and relapse rates; and (2) to describe their features. A systematic review was conducted following the internationally Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Of the total 6016 studies screened, 24 were included, of which nine used GSC-Apps and 15 FFSC-Apps. Eight studies reported significant differences between conditions in smoking cessation outcomes, with three of them being in favor of the use of apps, and two between different point-assessments. Concerning Apps features, most GSC-Apps included self-tracking and setting a quit plan, whereas most of the FFSC-Apps included self-tracking and carbon monoxide (CO) measures. Smartphone apps for smoking cessation could be promising tools. However, more research with an adequate methodological quality is needed to determine its effect. Nevertheless, smartphone apps’ high availability and attractiveness represent a great opportunity to reach large populations.

Prompt CR Plus Consolidation Therapy Yields Improve Survival after Allogeneic Transplantation for AML Patients Receiving Myeloablative, but Not Reduced-Intensity Conditioning: A CIBMTR Analysis

Leukemia relapse and treatment related mortality (TRM) remain major obstacles for successful allogeneic hematopoietic cell transplantation (allo-HCT). The number of induction cycles using intensive chemotherapy at AML diagnosis to achieve complete remission (CR) and the number of consolidation cycles and disease status at the time of allo-HCT for patients with acute myeloid leukemia (AML) may each affect TRM and relapse rates. We investigated the impact of the number of induction/consolidation cycles and disease status on the success of allo-HCT in 3113 AML patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) (2008-2019). They received allo-HCT in first CR or with persistent leukemia (primary induction failure-PIF) receiving myeloablative (MA) or reduced-intensity (RIC) conditioning. 1473 AML patients (median age, 47 years) in CR received MAC; 862 (58%) achieved CR after 1 cycle of intensive induction chemotherapy and 74% of these had no evidence of measurable residual disease (MRD). 454 (31%) patients required 2 cycles to CR (72 % MRD negative) and 157 (11%) patients (69% MRD negative) after ≥ 3 cycles. The overall survival (OS), relapse and TRM by induction cycle number is shown in Table 1. Multivariate analysis demonstrated that CR after 1 cycle led to higher OS vs. 2 cycles (HR 1.32 95%CI 1.11-1.56, p< 0.01) or ≥ 3 cycles (HR 1.47 95%CI 1.16-1.87, p< 0.01), while OS after 2 cycles or ≥ 3 cycles were similar (HR 1.2 95%CI 0.87-1.4, p=0.38). Higher TRM was observed in patients receiving 2 or ≥ 3 cycles vs. only 1 induction cycles (HR 1.34 95%CI 1.05-1.72, p< 0.02). Relapse risk was greater in those needing ≥ 3 cycles to achieve CR. Consolidation therapy after CR was associated with improved OS vs. no consolidation therapy (HR 1.57 95%CI 1.24-1.99, p< 0.01). The need for ≥2 induction cycles plus consolidation therapy was associated with higher TRM (HR 1.34 95%CI 1.05-1.72, p< 0.02). 1162 AML patients (median age, 63 years) in CR received allo-HCT after RIC; 714 (61%) achieved CR after 1 cycle of induction chemotherapy (72% MRD negative); 310 (27%) patients after 2 cycles (67% MRD negative) and 138 (12%) patients (58% MRD negative) after ≥ 3 cycles (Table 1). Multivariate analysis demonstrated that the number of induction cycles did not affect the OS or TRM. Relapse risk was greater in patients requiring ≥2 cycles to achieve CR. The use of consolidation therapy did not affect OS or TRM. MRD status at the time of allo-HCT did not have a significant impact on OS, TRM and relapse rates after either MA or RIC conditioning. 478 AML patients received allo-HCT after PIF (328 patients with MAC [median age, 51 years], 150 patients RIC [median age, 61 years], Table 1). After MAC, OS and relapse were significantly worse in PIF patients compared to any CR patients (p<0.01). After RIC, relapse was significantly more frequent in PIF patients vs. CR patients after 1 or more induction cycles (p<0.01). TRM was similar for PIF vs CR patients after MAC or RIC allo-HCT. These data demonstrate that among patients eligible for allo-HCT, the need for only one induction cycle to achieve CR, particularly when combined with consolidation therapy is associated with better outcomes after MA conditioning. Achieving CR prior to allo-HCT needing one or more induction cycles is associated with lower relapse rates and improved OS compared to patients with PIF that receive allo-HCT. Figure 1 Figure 1. Disclosures de Lima: BMS: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotec: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Hourigan: Govt. COI: Other. Litzow: Omeros: Other: Advisory Board; Pluristem: Research Funding; Jazz: Other: Advisory Board; AbbVie: Research Funding; Amgen: Research Funding; Actinium: Research Funding; Astellas: Research Funding; Biosight: Other: Data monitoring committee. Saber: Govt. COI: Other. Weisdorf: Incyte: Research Funding; Fate Therapeutics: Research Funding.