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The Cochrane Database of Systematic... Dec 2016Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy, the majority of which may be able to achieve remission with a single antiepileptic drug (AED).The correct choice of first-line antiepileptic therapy for individuals with newly diagnosed seizures is of great importance. It is important that the choice of AED for an individual is based on the highest-quality evidence available regarding the potential benefits and harms of various treatments. It is also important to compare the efficacy and tolerability of AEDs appropriate to given seizure types.Topiramate and carbamazepine are commonly used AEDs. Performing a synthesis of the evidence from existing trials will increase the precision of results of outcomes relating to efficacy and tolerability, and may help inform a choice between the two drugs.
OBJECTIVES
To assess the effects of topiramate monotherapy versus carbamazepine monotherapy for epilepsy in people with partial-onset seizures (simple or complex partial and secondarily generalised) or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
SEARCH METHODS
We searched the Cochrane Epilepsy Group Specialized Register (14 April 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (14 April 2016) and MEDLINE (Ovid, 1946 to 14 April 2016). We imposed no language restrictions. We also contacted pharmaceutical companies and trial investigators.
SELECTION CRITERIA
Randomised controlled trials in children or adults with partial-onset seizures or generalised-onset tonic-clonic seizures with or without other generalised seizure types with a comparison of monotherapy with either topiramate or carbamazepine.
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) review. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to first seizure post randomisation', 'time to 6-month remission, 'time to 12-month remission' and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs), and used the generic inverse variance method to obtain the overall pooled HRs and 95% CIs.
MAIN RESULTS
IPD were available for 1151 of 1239 eligible individuals from two of three eligible studies (93% of the potential data). A small proportion of individuals recruited into these trials had 'unclassified seizures;' for analysis purposes, these individuals are grouped with those with generalised onset seizures. For remission outcomes, a HR < 1 indicated an advantage for carbamazepine, and for first seizure and withdrawal outcomes, a HR < 1 indicated an advantage for topiramate.The main overall results, given as pooled HR adjusted for seizure type (95% CI) were: for time to withdrawal of allocated treatment 1.16 (0.98 to 1.38); time to first seizure 1.11 (0.96 to 1.29); and time to 6-month remission 0.88 (0.76 to 1.01). There were no statistically significant differences between the drugs. A statistically significant advantage for carbamazepine was shown for time to 12-month remission: 0.84 (0.71 to 1.00).The results of this review are applicable mainly to individuals with partial-onset seizures; 85% of included individuals experienced seizures of this type at baseline. For individuals with partial-onset seizures, a statistically significant advantage for carbamazepine was shown for time to withdrawal of allocated treatment (HR 1.20, 95% CI 1.00 to 1.45) and time to 12-month remission (HR 0.84, 95% CI 0.71 to 1.00). No statistically significant differences were apparent between the drugs for other outcomes and for the limited number of individuals with generalised-onset tonic-clonic seizures with or without other generalised seizure types or unclassified seizures.The most commonly reported adverse events with both drugs were drowsiness or fatigue, 'pins and needles' (tingling sensation), headache, gastrointestinal disturbance and anxiety or depression The rate of adverse events was similar across the two drugs.We judged the methodological quality of the included trials generally to be good; however, there was some evidence that the open-label design of the larger of the two trials may have influenced the withdrawal rate from the trial. Hence, we judged the evidence for the primary outcome of treatment withdrawal to be moderate for individuals with partial-onset seizures and low for individuals with generalised-onset seizures. For efficacy outcomes (first seizure, remission), we judged the evidence from this review to be high for individuals with partial-onset seizures and moderate for individuals with generalised-onset or unclassified seizures.
AUTHORS' CONCLUSIONS
For individuals with partial-onset seizures, there is evidence that carbamazepine is less likely to be withdrawn and that 12-month remission will be achieved earlier than with topiramate. No differences were found between the drugs in terms of the outcomes measured in the review for individuals with generalised tonic-clonic seizures with or without other seizure types or unclassified epilepsy; however, we encourage caution in the interpretation of these results due to the small numbers of participants with these seizure types.We recommend that future trials should be designed to the highest quality possible and take into consideration masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.
Topics: Anticonvulsants; Carbamazepine; Epilepsies, Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Fructose; Humans; Induction Chemotherapy; Topiramate
PubMed: 27922722
DOI: 10.1002/14651858.CD012065.pub2 -
Journal of the American Society of... Mar 2017Although change in proteinuria has been proposed as a surrogate for long-term prognosis in membranous nephropathy (MGN), variability in proteinuria levels and lag...
Although change in proteinuria has been proposed as a surrogate for long-term prognosis in membranous nephropathy (MGN), variability in proteinuria levels and lag between these changes and acceptable end points, such as ESRD, has limited its utility. This cohort study examined the prognostic significance of remission duration in 376 patients with biopsy-proven idiopathic/primary MGN who achieved a remission after a period of nephrotic-range proteinuria. We defined complete remission (CR), partial remission (PR), and relapse as proteinuria ≤0.3, 0.4-3.4, and ≥3.5 g/d after CR or PR, respectively. The exposure variable was the remission status of patients at fixed landmarks (3, 6, 12, 24, and 36 months) after the date of first remission. The primary outcome was ESRD or 50% reduction in eGFR. We fitted Cox proportional hazards models to examine the association of remission status at each landmark and the primary end point. Persistent remission associated with unadjusted hazard ratios for the primary outcome that ranged by landmark from 0.35 (95% confidence interval, 0.20 to 0.61) to 0.56 (95% confidence interval, 0.31 to 1.04). Separate analyses for PR and CR yielded similar results. After adjustment, maintaining remission associated with significantly reduced risk of the primary outcome at all landmarks. Durable remissions associated with improved renal survival. Although the longer the remission, the greater the improvement, patients with remission durations as short as 3 months had improved renal prognosis compared with patients who relapsed. This study validates and quantifies PR and CR as surrogates for long-term outcome in MGN.
Topics: Cohort Studies; Female; Glomerulonephritis, Membranous; Humans; Male; Middle Aged; Prognosis; Proteinuria; Remission Induction; Time Factors; Treatment Outcome
PubMed: 27756808
DOI: 10.1681/ASN.2015111262 -
Annals of Oncology : Official Journal... Jul 2011T-cell lymphomas are a heterogeneous group of non-Hodgkin's lymphomas (NHLs). With the exception of anaplastic lymphoma kinase protein-positive large-cell lymphoma,... (Review)
Review
BACKGROUND
T-cell lymphomas are a heterogeneous group of non-Hodgkin's lymphomas (NHLs). With the exception of anaplastic lymphoma kinase protein-positive large-cell lymphoma, standard chemotherapy provides dismal long-term outcomes when compared with NHLs with B-cell immunophenotype.
DESIGN
We review the literature on the role of high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in T-cell NHLs both as up-front treatment and in the salvage setting. The role of allogeneic transplantation will also be reviewed.
RESULTS
Results from five prospective, nonrandomized and six retrospective studies evaluating the role of HDT and ASCT in the up-front setting show that patients in first complete or partial remission especially those who present with advanced disease and high prognostic index of peripheral T-cell lymphoma score may benefit from this approach. In the relapsed and/or refractory setting, most series show results that are comparable with those seen in patients with B-cell lymphomas if transplanted with chemosensitive disease. There is limited evidence to suggest that an immune-mediated graft-versus-lymphoma effect may result in long-term disease remissions in some patients after allogeneic transplantation.
CONCLUSIONS
Randomized studies comparing HDT and ASCT with conventional chemotherapy are needed in T-cell lymphomas.
Topics: Humans; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Prognosis; Stem Cell Transplantation
PubMed: 21551006
DOI: 10.1093/annonc/mdr140 -
Cleveland Clinic Journal of Medicine 1993Approximately 6% of the population will experience at least one afebrile seizure in their lifetime. (Review)
Review
BACKGROUND
Approximately 6% of the population will experience at least one afebrile seizure in their lifetime.
OBJECTIVE
To review the prognostic factors and clinical implications for recurrence, remission, and relapse of seizures.
SUMMARY
Antiepileptic drug treatment reduces the risk of recurrence after a first seizure by about half, but these drugs cause a variety of adverse effects. The risk of recurrence is higher in the presence of neurologic or electroencephalographic abnormalities or if the seizure is partial as opposed to generalized. Neurologic abnormalities and partial seizures also reduce the probability of remission. Gradual drug withdrawal can be considered if the patient has been in remission for 2 years in the absence of any negative prognostic indicators.
CONCLUSIONS
When deciding whether to begin or discontinue antiepileptic drug therapy, clinicians should consider the risks and possible benefits for the individual patient.
Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Electroencephalography; Humans; Infant; Infant, Newborn; Middle Aged; Prognosis; Recurrence; Remission Induction; Risk Factors; Seizures; Time Factors
PubMed: 8287503
DOI: 10.3949/ccjm.60.6.439 -
Diabetes Care Aug 2009OBJECTIVE To find a simple definition of partial remission in type 1 diabetes that reflects both residual beta-cell function and efficacy of insulin treatment. RESEARCH...
OBJECTIVE To find a simple definition of partial remission in type 1 diabetes that reflects both residual beta-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS A total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual beta-cell function. RESULTS By multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient -0.21, P < 0.001) and insulin dose (-0.94, P < 0.001) was shown. These results suggested the definition of an insulin dose-adjusted A1C (IDAA1C) as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C < or =9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C < or =9 had a significantly higher agreement (P < 0.001) with residual beta-cell function than use of a definition of A1C < or =7.5%. Between 6 and 12 months after diagnosis, for IDAA1C < or =9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C < or =7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose < or =0.5 units . kg(-1) . 24 h(-1) 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (>300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months. CONCLUSIONS A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual beta-cell function and has better stability compared with the conventional definitions.
Topics: Adolescent; Aging; Body Mass Index; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Administration Schedule; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant; Insulin; Longitudinal Studies; Multivariate Analysis; Puberty; Regression Analysis; Remission, Spontaneous
PubMed: 19435955
DOI: 10.2337/dc08-1987 -
Clinical Journal of the American... Sep 2020C3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
C3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies showed that treatment with corticosteroids plus mycophenolate mofetil (MMF) was associated with improved outcomes, although the genetic profile of these patients was not systematically analyzed. This study aims to analyze the main determinants of disease progression and response to this therapeutic regimen.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We conducted a retrospective, multicenter, observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy (=81) or dense deposit disease (=16) between January 1995 and March 2018 were enrolled. Multivariable and propensity score matching analyses were used to evaluate the association of clinical and genetic factors with response to treatment with corticosteroids and MMF as measured by proportion of patients with disease remission and kidney survival (status free of kidney failure).
RESULTS
The study group comprised 97 patients (84% C3 glomerulopathy, 16% dense deposit disease). Forty-two patients were treated with corticosteroids plus MMF, and this treatment was associated with a higher rate of remission and lower probability of kidney failure (79% and 14%, respectively) compared with patients treated with other immunosuppressives (24% and 59%, respectively), or ecluzimab (33% and 67%, respectively), or conservative management (18% and 65%, respectively). The therapeutic superiority of corticosteroids plus MMF was observed both in patients with complement abnormalities and with autoantibodies. However, patients with pathogenic variants in complement genes only achieved partial remission, whereas complete remissions were common among patients with autoantibody-mediated forms. The main determinant of no remission was baseline proteinuria. Relapses occurred after treatment discontinuation in 33% of the patients who had achieved remission with corticosteroids plus MMF, and a longer treatment length of MMF was associated with a lower risk of relapse.
CONCLUSIONS
The beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Child; Complement C3; Disease Progression; Drug Therapy, Combination; Female; Glomerulonephritis; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Recurrence; Remission Induction; Retrospective Studies; Risk Factors; Spain; Time Factors; Treatment Outcome; Young Adult
PubMed: 32816888
DOI: 10.2215/CJN.15241219 -
Indian Journal of Nephrology 2022There is a paucity of clinical data on C1q nephropathy (C1qN) in children in India and Southeast Asia. This is the first detailed analysis conducted to elucidate the...
INTRODUCTION
There is a paucity of clinical data on C1q nephropathy (C1qN) in children in India and Southeast Asia. This is the first detailed analysis conducted to elucidate the prevalence, clinicopathological profile, and response to different immunosuppressives in children with C1qN in India.
MATERIALS AND METHODS
Detailed demographic profile, clinical features, urine and blood chemistries, kidney biopsy, and response to different immunosuppressives of the study participants were analyzed between August 2015 and October 2020 for steroid-dependent/-resistant nephrotic syndrome (NS).
RESULTS
C1qN was diagnosed in 16 (14.13%) of 113 children who underwent biopsy for steroid-dependent/-resistant NS. The mean age was 44 months (range 18-99 months) and male and female number was 12 (75%) and four (25%), respectively, and mean follow-up was 3.5 years. Eight (50%) had coexistent minimal-change nephrotic syndrome (MCNS) pattern, seven (43.7%) had focal segmental glomerulosclerosis (FSGS), and one (6.2%) had diffuse mesangial hypercellularity. Thirteen children had complete follow-up, of which eight (61.5%) and four (30.7%) cases presented as steroid-dependent and primary steroid-resistant NS, respectively, whereas one (7.6%) had joint pain with rashes. At presentation, seven (53.8%) had hypertension, 12 (92.3%) had nephrotic range proteinuria, and six cases (46.1%) had hematuria. Nine (75%) of 12 cases achieved complete remission with calcineurin inhibitor (CNI) therapy, and two were non responders, one was a partial responder, and one responded to mycophenolate. Of six FSGS cases, four had complete remission, one had partial remission, and one was in non-remission. Of six cases with MCNS, five had complete remission and one was in non-remission. Renal functions remained normal in all except one case who had progression to chronic kidney disease Stage 3.
CONCLUSION
One out of seven children with difficult NS can have underlying C1qN. CNIs are most beneficial to attain and maintain remission. Renal functions remain normal in the majority. Along with C1q deposits, MCNS and FSGS patterns are seen equally and respond almost similarly to CNIs.
PubMed: 35283565
DOI: 10.4103/ijn.IJN_578_20 -
BMJ Open Jun 2022Major depressive disorder (MDD) affects 163 million people globally every year. Individuals who experience subsyndromal depressive symptoms during remission (ie, partial...
Augmenting neurocognitive remediation therapy to Preventive Cognitive Therapy for partially remitted depressed patients: protocol of a pragmatic multicentre randomised controlled trial.
INTRODUCTION
Major depressive disorder (MDD) affects 163 million people globally every year. Individuals who experience subsyndromal depressive symptoms during remission (ie, partial remission of MDD) are especially at risk for a return to a depressive episode within an average of 4 months. Simultaneously, partial remission of MDD is associated with work and (psycho)social impairment and a lower quality of life. Brief psychological interventions such as preventive cognitive therapy (PCT) can reduce depressive symptoms or relapse for patients in partial remission, although achieving full remission with treatment is still a clinical challenge. Treatment might be more effective if cognitive functioning of patients is targeted as well since cognitive problems are the most persisting symptom in partial remission and predict poor treatment response and worse functioning. Studies show that cognitive functioning of patients with (remitted) MDD can be improved by online neurocognitive remediation therapy (oNCRT). Augmenting oNCRT to PCT might improve treatment effects for these patients by strengthening their cognitive functioning alongside a psychological intervention.
METHODS AND ANALYSIS
This study will examine the effectiveness of augmenting oNCRT to PCT in a pragmatic national multicentre superiority randomised controlled trial. We will include 115 adults partially remitted from MDD with subsyndromal depressive symptoms defined as a Hamilton Depression Rating Scale score between 8 and 15. Participants will be randomly allocated to PCT with oNCRT, or PCT only. Primary outcome measure is the effect on depressive symptomatology over 1 year. Secondary outcomes include time to relapse, cognitive functioning, quality of life and healthcare costs. This first dual approach study of augmenting oNCRT to PCT might facilitate full remission in partially remitted individuals as well as prevent relapse over time.
ETHICS AND DISSEMINATION
Ethical approval was obtained by Academic Medical Center, Amsterdam. Outcomes will be made publicly available.
TRIAL REGISTRATION NUMBER
NL9582.
Topics: Adult; Chronic Disease; Cognition; Cognitive Behavioral Therapy; Depressive Disorder, Major; Humans; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35738653
DOI: 10.1136/bmjopen-2022-063407 -
Annals of the New York Academy of... Sep 2002Malignant pheochromocytomas, a group of tumors that include metastatic paragangliomas, often produce hypertension and episodic symptoms from secretion of norepinephrine... (Review)
Review
Malignant pheochromocytomas, a group of tumors that include metastatic paragangliomas, often produce hypertension and episodic symptoms from secretion of norepinephrine and sometimes epinephrine. In addition, the tumors usually manifest progressive metastases. Blockade of alpha and beta adrenergic receptors will control blood pressure and symptoms, but reduction of the malignancy has been difficult to achieve. Meta-iodobenzylguanidine (MIBG) follows the pathways of norepinephrine and, when labeled with 131-I, will concentrate sufficiently in the pheochromocytoma to impart therapeutic radiation. More than 100 patients have received treatment with 131-I-labeled MIBG at multiple medical centers. Individual doses were 3.7 to 18.5 GBq (100 to >500 mCi), and many patients received several doses separated by a few months. Partial remissions, recorded as decreased tumor presence and tumor function, have been observed in one-third or more of the treated patients. However, complete remissions are rare, and recurrence/progression within two years is the rule. Toxicity was generally modest and temporary. Subsequent chemotherapy increased the benefits attained by 131-I MIBG, but, in a small series of patients, this combination did not further change the outcome. Nevertheless, selective radiation from 131-I MIBG or a similar radiopharmaceutical could play a valuable role in treatments that combine several types of attacks on this recalcitrant malignancy.
Topics: 3-Iodobenzylguanidine; Adrenal Gland Neoplasms; Antineoplastic Agents; Humans; Iodine Radioisotopes; Molecular Structure; Pheochromocytoma; Radiopharmaceuticals
PubMed: 12381541
DOI: 10.1111/j.1749-6632.2002.tb04412.x -
JID Innovations : Skin Science From... Dec 2021Bullous pemphigoid (BP) is an autoimmune blistering disease resulting in pruritus and cutaneous blistering. Longitudinal studies characterizing the disease course of...
Bullous pemphigoid (BP) is an autoimmune blistering disease resulting in pruritus and cutaneous blistering. Longitudinal studies characterizing the disease course of patients with BP on conventional therapy are lacking. We sought to characterize the changes in disease activity and pruritus of patients with BP on standard-of-care treatments. We conducted a retrospective cohort study on patients with BP on standard-of-care therapy. Generalized Estimating Equations were used to estimate the mean and standard errors for Bullous Pemphigoid Disease Activity Index (BPDAI) total activity score, BPDAI pruritus component score, and anti-BP180 autoantibody levels (BP180) over time. A total of 80 patients with BP showed consistent reductions in BPDAI total activity score and BPDAI pruritus component score, with a nadir at 4 months. BP180 decreased over time, with the largest reductions at 6 and 9 months. Median partial/complete remission was at 6.7 months, with relapses at a median time of 15.9 months. Receiving operating characteristic analysis determined an optimal BPDAI total activity score cutoff of 3.3 to discriminate partial/complete remission incidence (area under the curve = 0.895, sensitivity = 0.844, specificity = 0.78). In conclusion, in patients with BP on standard-of-care therapy, a natural course of BPDAI total activity score and BPDAI pruritus component score over time was comprehensively projected. BPDAI ≤ 3.3 was associated with partial/complete remission. These results provide reference data to guide future clinical trial design for BP.
PubMed: 34909747
DOI: 10.1016/j.xjidi.2021.100050