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Real world long-term outcomes in patients with mucopolysaccharidosis type II: A retrospective cohort study

ABSTRACT: Summary We investigated the decline of activities of daily living with symptomatic progression in patients with mucopolysaccharidosis type II (MPS II) and investigated the associated factors. Clinical data were retrospectively collected from the medical records of 28 patients with MPS II who visited our hospital between October 2007 and August 2019. Activities of daily living were assessed over time using a 5-point scale (from stage 1, indicating independent, to stage 5, indicating total assistance + medical care); the relationships of the interval years from stage 2 (mild symptoms) to stage 4 (total assistance) with therapeutic intervention, anti-drug antibodies (ADA), urinary glycosaminoglycans (uGAG), and genotypes were analyzed. Eight are attenuated types, and 20 are severe types. Further, 20 underwent enzyme replacement therapy (ERT) alone, 5 underwent hematopoietic stem cell transplantation (HSCT) alone, and 3 underwent both therapy. The mean interval years (standard deviation) from stage 2 to 4 was 3.5 (0.7) and 7.3 (3.3) in patients who started undergoing ERT (n = 6) and HSCT (n = 3) at stage 2, respectively, whereas it was 3.1 (1.5) in patients who received no treatment until they reached stage 4 (n = 8). The study findings revealed the process of changes in the activities of daily living over a long duration in patients with MPS II undergoing different treatments. In severe type, the activity deteriorated regardless of the stage at which ERT was initiated. The activity declined slower in patients who received HSCT at an early stage.

SUBMITTER: Tomita K

PROVIDER: S-EPMC8554623 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Mucopolysaccharidosis type II (MPS II) is a neurometabolic disorder, due to the deficit of the lysosomal hydrolase iduronate 2-sulfatase (IDS). This leads to a severe clinical condition caused by a multi-organ accumulation of the glycosaminoglycans (GAGs/GAG) heparan- and dermatan-sulfate, whose elevated levels can be detected in body fluids. Since 2006, enzyme replacement therapy (ERT) has been clinically applied, showing efficacy in some peripheral districts. In addition to clinical monitoring, GAG dosage has been commonly used to evaluate ERT efficacy. However, a strict long-term monitoring of GAG content and composition in body fluids has been rarely performed. Here, we report the characterization of plasma and urine GAGs in Ids knock-out (Ids-ko) compared to wild-type (WT) mice, and their changes along a 24-week follow-up, with and without ERT. The concentration of heparan-sulfate (HS), chondroitin-sulfate (CS), and dermatan-sulfate (DS), and of the non-sulfated hyaluronic acid (HA), together with their differentially sulfated species, was quantified by capillary electrophoresis with laser-induced fluorescence. In untreated Ids-ko mice, HS and CS + DS were noticeably increased at all time points, while during ERT follow-up, a substantial decrease was evidenced for HS and, to a minor extent, for CS + DS. Moreover, several structural parameters were altered in untreated ko mice and reduced after ERT, however without reaching physiological values. Among these, disaccharide B and HS 2s disaccharide showed to be the most interesting candidates as biomarkers for MPS II. GAG chemical signature here defined provides potential biomarkers useful for an early diagnosis of MPS II, a more accurate follow-up of ERT, and efficacy evaluations of newly proposed therapies. KEY MESSAGES : Plasmatic and urinary GAGs are useful markers for MPS II early diagnosis and prognosis. CE-LIF allows GAG structural analysis and the quantification of 17 different disaccharides. Most GAG species increase and many structural features are altered in MPS II mouse model. GAG alterations tend to restore to wild-type levels following ERT administration. CS+DS/HS ratio, % 2,4dis CS+DS, and % HS 2s are potential markers for MPS II pathology and ERT efficacy.

Project description:BackgroundKetamine has emerged as a promising pharmacotherapy for depression and other mental illnesses, and the intramuscular (IM) administration of ketamine is now offered at many North American outpatient psychiatric clinics. However, a characterization of the outpatient population receiving IM ketamine treatment and an evaluation of the real-world depression, anxiety, and safety outcomes of long-term psychiatric IM ketamine treatment has not been reported. This study aimed to evaluate the clinical characteristics, treatment patterns, clinical outcomes, and adverse events of patients receiving IM ketamine treatment.MethodsPatient data from the electronic health records of a private outpatient psychiatric clinic network in the United States were collected and analyzed retrospectively. Adults with any psychiatric diagnosis who received ketamine treatment only by IM administration from January 2018 to June 2021 were included. A total of 452 patients were included in the cohort.ResultsPatients receiving IM ketamine treatment had a mean of 2.8 (SD 1.4) psychiatric diagnoses. 420 (93%) patients had a diagnosis of major depressive disorder, 243 (54%) patients had a diagnosis of generalized anxiety disorder, and 126 (28%) patients had a diagnosis of post-traumatic stress disorder. Patients received a median of 4 (range 1-48) IM ketamine treatments. Median depression scores (PHQ-9) improved 38% from 16.0 (IQR 11.3-21.8) at baseline to 10.0 (IQR 6.0-15.0) at last treatment (p < .001). Median anxiety scores (GAD-7) improved 50% from 14.0 (IQR 8.0-17.0) at baseline to 7.0 (IQR 4.3-11.8) at last treatment (p < .001). With maintenance ketamine treatments, average improvements in depression (PHQ-9) and anxiety (GAD-7) scores of at least 4.7 and 4.9 points were maintained for over 7 months. An adverse event occurred during 59 of 2532 treatments (2.3%).ConclusionsIM ketamine is being utilized to treat psychiatric outpatients with multiple mental illnesses not limited to depression. Average depression and anxiety levels significantly improve throughout IM ketamine treatment and do not regress to baseline during patients' maintenance treatment phase. Prospective studies are recommended to confirm the long-term effectiveness and safety of IM ketamine.

Project description:OBJECTIVES:Rapid initiation of antiretroviral therapy (ART) engenders faster viral suppression but with suboptimal rates of durable viral suppression and engagement in care, as reported by clinical trials in resource-limited settings. Real-world experience with rapid ART initiation remains limited in resource-rich settings. DESIGN:Retrospective cohort study. SETTING:A tertiary hospital in metropolitan Taipei, Taiwan. PARTICIPANTS:We included 631 patients newly diagnosed as having HIV infection between March 2014 and July 2018. MAIN OUTCOME MEASURES:Rapid ART initiation was defined as starting ART within 7 days after HIV diagnosis confirmation. HIV diagnosis, ART initiation and viral suppression dates and clinical outcome data were collected by reviewing medical records. The rates of loss to follow-up (LTFU), engagement in care and virological rebound at 12 months were compared between patients with rapid ART initiation and those with standard initiation. RESULTS:Rapid ART initiation increased from 33.8% in 2014 to 68.3% in 2017, and the median interval between HIV diagnosis and viral suppression (HIV RNA load <200 copies/mL) decreased from 138 to 47 days. Patients with rapid ART initiation had a significantly higher rate of engagement in care at 12 months than did those with standard initiation (88.3% vs 79.0%; p=0.002). Patients aged <30 years had a higher risk of LTFU (HR: 2.19; 95% CI 1.20 to 3.98); and rapid ART initiation was associated with a lower risk of LTFU (HR: 0.41; 95%?CI 0.24 to 0.83). Patients aged <30 years were more likely to acquire incident sexually transmitted infections (STIs) before achieving viral suppression. CONCLUSIONS:Rapid ART initiation was associated with a higher rate of engagement in care at 12 months and shortened interval from diagnosis to HIV suppression. Delayed ART initiation may increase onwards HIV transmission considering the high rates of STIs. ETHICS APPROVAL:The study was approved by the Research Ethics Committee of National Taiwan University Hospital (Registration No. 201003112R).

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Real world long-term outcomes in patients with mucopolysaccharidosis type II: A retrospective cohort study

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