scholarly journals POS1091 KNEE JOINT DISTRACTION RESULTS IN MRI CARTILAGE THICKNESS INCREASE UP TO TEN YEARS AFTER TREATMENT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 825.1-825
Author(s):  
M. Jansen ◽  
S. Mastbergen ◽  
T. D. Turmezei ◽  
J. W. Mackay ◽  
F. Lafeber
Keyword(s):  
Cartilage Regeneration ◽  
Cartilage Thickness ◽  
Short Term ◽  
Thickness Increase ◽  
Time Points ◽  
Joint Distraction ◽  
Mri Scans ◽  
Pre Treatment ◽  
Changes Over Time

Background:Knee joint distraction (KJD) is a joint-preserving treatment option for younger (age <65 years) knee osteoarthritis (OA) patients. It has shown clinical improvement for up to nine years after treatment. Radiographs and MRI scans have previously shown cartilage regeneration activity, especially in the first two years after treatment. However, MRIs have not been evaluated more than five years after this treatment.Objectives:To evaluate MRI cartilage thickness up to ten years after KJD treatment.Methods:Patients (n=20) with end-stage knee OA, indicated for total knee arthroplasty (TKA) but <60 years old, were treated with KJD. 3T MRIs with 3D spoiled gradient recalled imaging sequence with fat suppression (SPGR-fs) were acquired before and one, two, five, seven and ten years after surgical treatment. Stradview v6.0 was used for semi-automatic cartilage segmentation; wxRegSurf v18 was used for surface registration. MATLAB R2020a and the SurfStat MATLAB package were used for data analysis and visualization. For changes over time, linear mixed models were used. Two separate linear regression models were used to show the influence of baseline Kellgren-Lawrence grade and sex on the changes over time. Statistical significance was calculated with statistical parametric mapping; a p-value <0.05 was considered statistically significant. Since KJD has previously shown significant results mostly in the patients’ most affected compartment (MAC), patients were separated in two groups based on whether their MAC was the medial or lateral compartment.Results:The MAC was predominantly the medial side (medial MAC n=18; lateral n=2). The 18 patients with a medial MAC all had MRI scans at baseline, one and two years after treatment. After two years, some patients were lost to follow-up, decreasing data availability at five (n=15), seven (n=11) and ten years (n=7). Figure 1 (top) shows the average cartilage thickness at the different time points for all medial MAC patients together. One and two years after treatment the cartilage in the medial weight-bearing region was on average thicker than before treatment. While from five years after treatment the cartilage thickness gradually decreased, even at ten years the medial cartilage thickness seemed slightly higher than pre-treatment. Figure 1 (bottom) shows cartilage thickness changes compared to baseline for patients with a medial MAC. Patients with a lateral MAC showed a similar pattern, with the biggest changes showing on the lateral side. As indicated by the dark blue areas, the medial femoral cartilage thickness increase, which was up to 0.5 mm after one year and 0.6 mm after two years, was largely statistically significant at both these time points. While the medial tibia showed an increase of up to 0.5 mm at these time points as well, this was not statistically significant at two years. Surprisingly, long-term results showed areas of the lateral (less affected) compartment were significantly thicker, up to 0.7 mm, compared to pre-treatment in both the femur and tibia compared to baseline. Kellgren-Lawrence grade and sex were shown to influence the changes, albeit not statistically significantly. Patients with a higher Kellgren-Lawrence grade and male sex showed a higher short-term (one and two year) but a lower long-term (seven and ten year) cartilage thickness increase.Conclusion:KJD treatment results in significant short-term cartilage regeneration in the most affected compartment. While after two years this initial gain in cartilage thickness is gradually lost, likely as a result of natural progression, even ten years after treatment the cartilage is thicker than before treatment. In the less affected compartment, a delayed cartilage response seems to take place, with significantly increased cartilage thickness in the long term. In conclusion, in these young OA patients indicated for TKA, KJD results in femoral and tibial cartilaginous tissue regeneration both short- and long-term and in both sides of the joint.Disclosure of Interests:None declared.

scholarly journals FRI0408 KNEE JOINT DISTRACTION AS TREATMENT FOR OSTEOARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 803.1-803
Author(s):  
M. Jansen ◽  
T. Boymans ◽  
R. Custers ◽  
R. Van Geenen ◽  
R. Van Heerwaarden ◽  
...  
Keyword(s):  
Knee Joint ◽  
Cartilage Thickness ◽  
Control Groups ◽  
Younger Patients ◽  
Time Points ◽  
Joint Distraction ◽  
Short And Long Term ◽  
Tract Infections

Background:Knee osteoarthritis (OA) is a common cause of invalidity and is often treated with a total knee arthroplasty (TKA). While TKA is cost-effective, reduces pain and improves function, it brings a greater risk of a future revision surgery when performed in younger patients. Knee joint distraction (KJD) is a joint-preserving OA treatment that may postpone TKA and possibly prevent a revision. In the past years, multiple studies have investigated this surgical treatment.Objectives:To evaluate short- and long-term clinical benefit and tissue structure changes after KJD treatment for knee OA.Methods:MEDLINE, EMBASE and Web of Science were searched for eligible clinical studies evaluating a change in at least one of: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Score of pain (VAS-pain), Knee injury and Osteoarthritis Outcome Score (KOOS), EuroQol-5D (EQ5D), radiographic joint space width (JSW) or MRI cartilage thickness after KJD. The primary clinical and structural outcome parameters were the WOMAC and minimum JSW, respectively. Random effects models were applied on all outcome parameters and outcomes were compared with control groups found in the included studies. For continuous data the mean difference (MD) and 95% confidence interval (95%CI) were calculated and for dichotomous data the risk difference and 95%CI, following the Cochrane handbook.Results:In total 11 articles reporting on 7 different KJD cohorts with in total 127 patients and 5 control groups at multiple follow-up moments were included, with 2 of the studies being randomized controlled trials (RCTs). The WOMAC (figure 1) was compared to pre-treatment in 3 cohorts after 1 year (patients n=62) and 2 years (n=59) and in 1 cohort after 5 years (n=20) and 9 years (n=8), showing a significant increase at all time points (all p<0.001). The VAS-pain showed similar results at the same 4 time points, as did the KOOS and EQ5D, which were evaluated only after 1 (n=42) and 2 (n=39) years.The minimum (figure 2) and mean JSW are reported in 3 cohorts after 1 (n=59) and 2 (n=59) years and in 1 cohort after 5 (n=20) and 7 (n=8) years. Both JSW measures were statistically significantly increased after 1 and 2 years, but after 5 and 7 years the JSW increase was no longer statistically significant. Similarly, the MRI cartilage thickness showed an increase at 1 and 2 years, but not at 5 years (all n=20).Complications were reported in 5 studies with 87 patients, with 57 patients developing one or more pin tract skin infections, giving a risk of pin tract infections of 63% (95%CI 45-81), the majority of which could be treated with oral antibiotics. Only a small amount of other complications occurred and were all treated successfully.Overall, clinical and structural outcomes were comparable with control groups, including high tibial osteotomy and TKA as compared after 1 and 2 years in the two RCTs. Apart from pin tract infections, complications were not different in severity and number between control groups and KJD.Conclusion:KJD causes clear benefit in clinical and structural parameters over time, short- and long-term. Although the total number of patients is limited, effect sizes are large. Longer follow-up with more patients is necessary and could improve patient selection for this intensive treatment, while preventing pin tract infections could lighten the patients’ treatment burden. Irrespectively, KJD provides an additional option in joint-preserving treatments for OA and a viable alternative to joint replacement, especially in younger patients.Figure:Disclosure of Interests:Mylène Jansen: None declared, Tim Boymans: None declared, Roel Custers: None declared, Rutger Van Geenen: None declared, Ronald Van Heerwaarden: None declared, Maarten Huizinga: None declared, Jorm Nellensteijn: None declared, Rob Sollie: None declared, Sander Spruijt Consultant of: Consultancy to Zimmer Biomet Inc., Simon Mastbergen: None declared

Knee joint distraction results in MRI cartilage thickness increase up to ten years after treatment

2021 ◽  
Vol 29 ◽  
pp. S331-S332
Author(s):  
M. Jansen ◽  
S.C. Mastbergen ◽  
T.D. Turmezei ◽  
J.W. MacKay ◽  
F.P. Lafeber
Keyword(s):  
Knee Joint ◽  
Cartilage Thickness ◽  
Thickness Increase ◽  
Joint Distraction

Patterns of long-term and short-term responses in adult patients with attention-deficit/hyperactivity disorder in a completer cohort of 12 weeks or more with atomoxetine

2015 ◽  
Vol 30 (8) ◽  
pp. 1011-1020 ◽  
Author(s):  
E. Sobanski ◽  
S. Leppämäki ◽  
C. Bushe ◽  
L. Berggren ◽  
M. Casillas ◽  
...  
Keyword(s):  
Adult Adhd ◽  
Term Treatment ◽  
Response Patterns ◽  
Clustering Methods ◽  
Short Term ◽  
Time Points ◽  
Hierarchical Clustering Methods ◽  
Mixed Modelling ◽  
L1 And L2

AbstractBackgroundAtomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns.MethodsFrom 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD who completed atomoxetine treatment at long-term (24 weeks; n = 1443) and/or short-term (12 weeks; n = 2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling.ResultsBased on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24 weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term (12 weeks) treatment. Four of the 5 long-term clusters (comprising 95% of completer patients) showed positive trajectories: 2 faster responding clusters (L1 and L2), and 2 more gradually responding clusters (L3 and L4). Responses (i.e. ≥ 30% reduction in CAARS-Inv:SV total score, and CGI-S score ≤ 3) were observed at 8 and 24 weeks in 80% and 95% of completers in Cluster L1, versus 5% and 48% in Cluster L4.ConclusionsWhile many adults with ADHD responded relatively rapidly to atomoxetine, others responded more gradually without a clear plateau at 24 weeks. Longer-term treatment may be associated with greater numbers of responders.

scholarly journals The Impact of Feedback Frequency on Performance in a Novel Speech Motor Learning Task

2017 ◽  
Vol 60 (6S) ◽  
pp. 1712-1725 ◽  
Author(s):  
Mara Steinberg Lowe ◽  
Adam Buchwald
Keyword(s):  
Motor Learning ◽  
Learning Task ◽  
Short Term ◽  
Time Points ◽  
Term Retention ◽  
Long Term Retention ◽  
Speech Motor Learning ◽  
The Impact ◽  
Speech Motor

Purpose This study investigated whether whole nonword accuracy, phoneme accuracy, and acoustic duration measures were influenced by the amount of feedback speakers without impairment received during a novel speech motor learning task. Method Thirty-two native English speakers completed a nonword production task across 3 time points: practice, short-term retention, and long-term retention. During practice, participants received knowledge of results feedback according to a randomly assigned schedule (100%, 50%, 20%, or 0%). Changes in nonword accuracy, phoneme accuracy, nonword duration, and initial-cluster duration were compared among feedback groups, sessions, and stimulus properties. Results All participants improved phoneme and whole nonword accuracy at short-term and long-term retention time points. Participants also refined productions of nonwords, as indicated by a decrease in nonword duration across sessions. The 50% group exhibited the largest reduction in duration between practice and long-term retention for nonwords with native and nonnative clusters. Conclusions All speakers, regardless of feedback schedule, learned new speech motor behaviors quickly with a high degree of accuracy and refined their speech motor skills for perceptually accurate productions. Acoustic measurements may capture more subtle, subperceptual changes that may occur during speech motor learning. Supplemental Materials https://doi.org/10.23641/asha.5116324

scholarly journals DDEL-09. HIGH DOSE MTX110 (SOLUBLE PANOBINOSTAT) SAFELY ADMINISTERED INTO THE FOURTH VENTRICLE IN A NON-HUMAN PRIMATE MODEL

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii285-iii285
Author(s):  
Rachael W Sirianni ◽  
Natasha Kharas ◽  
Bangning Yu ◽  
Christopher F Janssen ◽  
Amanda Trimble ◽  
...  
Keyword(s):  
Fourth Ventricle ◽  
High Dose ◽  
Short Term ◽  
Primate Model ◽  
Lumbar Drain ◽  
Group I ◽  
Term Administration ◽  
Mri Scans ◽  
Group Ii

Abstract OBJECTIVE This study tested the safety and pharmacokinetics of short-term and long-term administration of MTX110 (soluble panobinostat; Midatech Pharma, UK) into the fourth ventricle of non-human primates. METHODS Four rhesus macaque monkeys underwent posterior fossa craniectomy and catheter insertion into the fourth ventricle. In Group I (n=2), catheters were externalized and lumbar drain catheters were placed simultaneously to assess cerebrospinal fluid (CSF) distribution after short-term infusions. MTX110 (0.5 ml of 300 μM panobinostat solution) was infused into the fourth ventricle daily for five consecutive days. Serial CSF and serum panobinostat levels were measured. In Group II (n=2), fourth ventricle catheters were connected to a subcutaneously-placed port for subsequent long-term infusions. Four cycles of MTX110, each consisting of 5 daily infusions (0.5 ml of 300 μM panobinostat solution), were administered over 8 weeks. Animals underwent detailed neurological evaluations, MRI scans, and post-mortem histological analysis. RESULTS Neurological assessments, MRI, and histology confirmed catheter placement and an absence of neurotoxicity. Panobinostat was undetectable in serum collected two and four hours after infusions in all samples in both groups. In Group I, mean peak panobinostat level in fourth ventricle CSF (6242 ng/ml) was significantly higher than in lumbar CSF (9 ng/ml; p &lt; 0.0001). In Group II, mean peak CSF panobinostat level (11,042 ng/ml) was significantly higher than mean trough CSF level (33 ng/ml; p&lt;0.0001). CONCLUSION MTX110 can be safely delivered via 4th ventricle at supra-therapeutic doses. These results provide data for a pilot clinical trial in patients with recurrent medulloblastoma.

scholarly journals THU0060 KNEE JOINT DISTRACTION INDUCED SHIFT FROM CATABOLIC TO ANABOLIC STATE OCCURS AFTER DISTRACTION PERIOD

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 242.1-242
Author(s):  
M. Teunissen ◽  
J. Popov-Celeketic ◽  
K. Coeleveld ◽  
B. Meij ◽  
F. Lafeber ◽  
...  
Keyword(s):  
Knee Joint ◽  
Matrix Protein ◽  
Collagen Type ◽  
Cartilage Damage ◽  
Cartilage Regeneration ◽  
Synthesis Rate ◽  
Mixed Response ◽  
Joint Distraction

Background:Knee joint distraction (KJD) is a validated joint-preserving treatment strategy for severe osteoarthritis (OA) that provides long-term clinical and structural improvement. Human trials and animal models indicate clear cartilage regeneration from 6 months and onwards post-KJD [1]. Recent work showed that during distraction, the balance between catabolic and anabolic indicators is directed towards catabolism, as indicated by collagen type 2 markers, proteoglycan (PG) turnover and a catabolic transcription profile.Objectives:To investigate the cartilage changes directly and 10 weeks after joint distraction in order to elucidate the shift from a catabolic to an anabolic cartilage state.Methods:Knee OA was induced bilaterally in 8 dogs according to the groove model. After 10 weeks of OA induction, all 8 animals were treated with knee joint distraction, employing the left knee as an OA control. After 8 weeks of distraction, 4 dogs were euthanized (KJDdirect) and after 10 weeks of follow-up the 4 remaining dogs (KJD+10). Macroscopic and microscopic cartilage degeneration was assessed using the OARSI canine scoring system. RT-qPCR was used to determine relative expression of aggrecan (ACAN)¸collagen type II(COL2α1), cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase-3 (MMP3) in the cartilage. PG content was determined by the Alcian Blue assay and the synthesis of PGs was determined using35SO42-as a tracer, as published before.Results:Macroscopic cartilage damage of the tibial plateau in the KJDdirectgroup was higher as compared to the OA control (OARSI score: 1.7±0.2 vs 0.6±0.3;p < 0.001). For KJD+10this difference persisted (OARSI score: 1.4±0.6 vs 0.6±0.3;p = 0.05). Microscopically, an increase in the total OARSI score was seen after 10 weeks post-KJD. This was mainly due to an increase of chondrocyte clusters at 10 weeks of follow-up, resulting in an increased sub score chondrocyte pathology. Remarkedly the sub score intensity of proteoglycan staining decreased directly after KJD (indicating a loss of PGs) but increased after 10 weeks of follow-up suggesting a mixed response depending on the item scored.Cartilage gene expression analysis showed downregulation ofCOL2α1(-1.3 ± 0.3), ACAN(-4.4 ± 1.0,p < 0.01) andCOMP(-1.7 ± 0.5) in thetgroup compared to OA control suggesting enhanced catabolic activity during KJD. In contrast, after 10 weeks of follow-up the expression ofCOL2α1andCOMPwere increased as compared to the OA control (2.6 ± 1.1 and 2.5 ± 1.2 respectively) as well as compared to the KJDdirecsituation (3.3 ± 1.4 and 4.2 ± 2.0).Expression ofMMP3was upregulated directly after KJD (4.4 ± 0.8) and downregulated after 10 weeks of follow up (-3.3 ± 0.8).Biochemical analysis of the tibia cartilage of the KJDdirectgroup revealed a lower PG content compared to the OA joint (20.1±10.3 mg/g vs 23.7±11.7 mg/g). At 10 weeks post-KJD this difference in PG content was gone (24.8±6.8 mg/g vs 25.4±7.8 mg/g). The PG synthesis rate directly after KJD appeared significantly lower vs. OA (1.4±0.6 nmol/h.g vs 5.9±4.4 nmol/h.g;p < 0.001)). 10 weeks post-KJD this difference was not detected (3.7±1.2 nmol/h.g vs 2.9±0.8 nmol/h.g), and the synthesis rate in the distracted knee was increased compared to directly after distraction (p < 0.01) indicating a shift upon follow-up.Conclusion:Further in-depth investigation of the material is ongoing and also includes the other joint tissues such as the bone and the synovial tissue. Irrespective, these first results on cartilage changes suggest that the shift from a catabolic to an anabolic state occurs within the weeksafterjoint distraction. As such, the post-distraction period seems to be essential in identifying key-players that support intrinsic cartilage repair.References:[1]Mastbergen SC, Nat Rev Rheumatol. 2013 May;9(5):277-90.Acknowledgments:TTW Technology Foundation: Perspectief P15-23, Dutch Arthritis Society: Long term Research Program LLP9Disclosure of Interests:Michelle Teunissen: None declared, Jelena Popov-Celeketic: None declared, Katja Coeleveld: None declared, Bjorn Meij: None declared, Floris Lafeber Shareholder of: Co-founder and shareholder of ArthroSave BV, Marianna Tryfonidou: None declared, Simon Mastbergen: None declared

scholarly journals Direct-acting Antivirals in Kidney Transplant Patients: Successful Hepatitis C Treatment and Short Term Reduction in Urinary Protein/Creatinine Ratios

2017 ◽  
Vol 2 (3) ◽  
pp. 366 ◽  
Author(s):  
Michael R. Goetsch ◽  
Ashutosh Tamhane ◽  
Mohit Varshney ◽  
Anuj Kapil ◽  
Edgar T. Overton ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Post Treatment ◽  
Kidney Graft ◽  
Direct Acting Antivirals ◽  
Short Term ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Pre Treatment ◽  
Direct Acting

Introduction: The role of Hepatitis C Virus (HCV) clearance in long-term kidney graft survival is unknown. In this study, we examined short-term trends of urinary protein/creatinine (P/C) ratios in a cohort of HCV-infected kidney transplant recipients with stable graft function and treated with direct-acting antivirals (DAAs).Methods: We conducted a retrospective study of 19 kidney transplant patients with chronic HCV infection treated with DAAs at the University of Alabama at Birmingham 1917 Viral Hepatitis Clinic between January 2013 and June 2016. Markers of glomerular damage were assessed using average protein/creatinine (P/C) ratios measured pre- and post-treatment. We also described treatment efficacy using sustained virologic response at 12 weeks post-HCV treatment (SVR12).Results: The median age of the 19 patients included was 59 years (Q1=58, Q3=64) at completion of treatment. Of these patients, 68% were African American, 32% were White and 63% were male. The median time between kidney transplant and initiation of DAA therapy was 2.25 years (Q1=0.79, Q3=3.79). Post-treatment P/C ratios (median=0.127, Q1=0.090, Q3=0.220) were significantly lower (p=0.01) than pre-treatment ratios (median=0.168, Q1=0.118, Q3=0.385). P/C ratios decreased in 14 of 19 patients (74%) with median change of -0.072 (median percent change= -40%). Post-treatment eGFRs (median=58.9, Q1=48.9, Q3=72.3) were not significantly different (p=0.82) than the pre-treatment values (median=57.0, Q1=48.8, Q3=67.8).Conclusions: In this preliminary study, there was a statistically significant decrease in P/C ratios associated with HCV clearance, suggesting a potential role for DAAs in improving kidney graft survival. Larger cohort studies will be needed to assess the clinical and long-term benefits of DAAs in this special population of HCV infected patients. 

The response of defoliated swards of subterranean clover to temperature

1976 ◽  
Vol 27 (5) ◽  
pp. 593 ◽  
Author(s):  
EAN Greenwood ◽  
BA Carbon ◽  
RC Rossiter ◽  
JD Beresford
Keyword(s):  
Subterranean Clover ◽  
Trifolium Subterraneum ◽  
Dry Weight ◽  
Carbon Dioxide Exchange ◽  
Short Term ◽  
Plant Parts ◽  
Pre Treatment ◽  
Reproductive Phases ◽  
Whole Life Cycle

The objective was to characterize the response of Trifolium subterraneum L. (cv. Daliak) swards to short-term and to long-term changes in temperature at several stages of plant growth. Short-term responses were studied with microswards growing in boxes in the open and defoliated every week to simulate heavy grazing. At seven stages, one subsample of boxes was harvested and three other subsamples were moved to controlled-temperature glasshouses and grown for 14 days at 10/5° (day/night), 17.5/12.5° and 25/20°C respectively, and then harvested. Dry weights and numbers of plant parts, and areas of leaves, height, light penetration and net carbon dioxide exchange of swards were measured. For long-term responses, young, defoliated microswards were transferred to the above temperatures for 9 weeks and cut weekly. On days 32 (pre-treatment harvest), 53, 74 and 95, tops and roots were harvested. The results support three generalizations. Firstly, severely defoliated subterranean clover pastures respond to temperature between 10/5° and 25/20° in a variety of ways over the whole life cycle. However, temperature is of greater importance as a determinant of dry weight of tops during the post-emergence and reproductive phases than it is during the preflowering phase. Secondly, total growth rate (TGR) after the first 8–10 weeks of growth does not increase at temperatures above 10/5°. And thirdly, even with moderately low LAI values of 1–4, temperatures of 25/20° can inhibit TGR after about 8 weeks of growth. The biological and agricultural implications are discussed.

The predictive value of gadolinium enhancement for long term disability in relapsing-remitting multiple sclerosis-preliminary results

2001 ◽  
Vol 7 (1) ◽  
pp. 23-25 ◽  
Author(s):  
N A Losseff ◽  
D H Miller ◽  
D Kidd ◽  
A J Thompson
Keyword(s):  
Multiple Sclerosis ◽  
Median Number ◽  
Short Term ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Relapsing Remitting Multiple Sclerosis

As short-term MRI studies are increasingly being used to monitor disease activity in multiple sclerosis (MS) it is vital to establish if short-term MRI activity is predictive of long term clinical outcome. We followed up after 5 years a group of 10 benign (relapsing-remitting MS with a disease duration 410 years and EDSS 43) and 10 early relapsing-remitting patients who previously had monthly serial MRI scans for 6 months. In the early relapsing-remitting group median EDSS at entry to the initial serial study was three and in the benign group 2.5. At 5-year follow up, five of these 20 patients had developed a definite deterioration in EDSS. The median number of new enhancing lesions detected originally in the group that had deteriorated was 11 (7-17) compared to 0 (0-5) new enhancing lesions, for those who had not deteriorated (P50.05). There was a trend towards a higher baseline T2 lesion load in the group with a definite change in EDSS but this was not significant. This study suggests that short-term measurement of the number of gadolinium enhancing lesions may predict long term outcome in relapsing-remitting MS.

Early glycaemic changes after initiation of oral antidiabetic medication and risk of major adverse cardiovascular events: results from a large primary care population of patients with type 2 diabetes

2020 ◽  
Author(s):  
Jonas Ghouse ◽  
Paul Blanche ◽  
Morten W Skov ◽  
Bent Lind ◽  
Allan Vaag ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Short Term ◽  
Oral Antidiabetic ◽  
Steep Decline ◽  
Pre Treatment ◽  
First Time

Abstract Aims To determine the risk of major adverse cardiovascular events (MACE) and death, associated with an early large and rapid decline in glycated haemoglobin (HbA1C) following first time initiation of an oral antidiabetic drug (OAD). Methods and results We included 10 518 primary care patients with type 2 diabetes, who initiated an OAD for the first time. For each individual, we measured a decline in HbA1C, as the difference between the pre-treatment HbA1C (within 3 months before OAD initiation) and the post-treatment HbA1C (within 1.5–4.5 months after OAD initiation), divided by the time between the two measurements. The decline was reported in mmol/mol change per 3 months in HbA1C and categorized by the median decline into levels of steep [≥9 mmol/mol (≥0.8%)] and flat decline [&lt;9 mmol/mol per 3 months (&lt;0.8%)]. Pre-treatment HbA1C was categorized by the median, into levels of low (48–62 mmol/mol) and high (&gt;62 mmol/mol). Multiple Cox regression was used to study the effect of decline (steep vs. flat) on the outcome hazard rates separately for patients with low and high pre-treatment HbA1C. Analyses were adjusted for age, sex, traditional cardiovascular risk factors, severe comorbidities, and concomitant medication treatment. During a median follow-up time of 7.7 years, 1625 developed MACE and 2323 died. We found that a steep decline vs. a flat decline was significantly associated with a decreased hazard for MACE, both in individuals with high [hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.69–0.94; P = 0.005] and low pre-treatment HbA1C (HR 0.79; 95% CI 0.66–0.96; P = 0.015). The hazard of MACE was more pronounced on the short-term vs. long-term in individuals with high pre-treatment HbA1C. We found no significant association between combinations of pre-treatment HbA1C and decline categories and hazard of all-cause mortality. However, a combination of a low pre-treatment HbA1C and steep decline was associated with increased 1-year mortality (HR 1.52; 95% CI 1.00–2.29; P = 0.048) and hypoglycaemia (HR 1.82; 95% CI 1.11–2.98; P = 0.017). Conclusion A combination of a high pre-treatment HbA1C and a steep decline in HbA1C was associated with a decreased short-term risk of MACE. A low pre-treatment HbA1C and a steep decline was associated with a long-term reduced risk of MACE, but a short-term increased risk of death and hypoglycaemia.

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