Enteroviral Meningitis: Natural History and Outcome of Pleconaril Therapy

ABSTRACT Enteroviral meningitis causes appreciable morbidity in adults, including hospitalization, decreased activity, and headache. Limited data define the natural history of disease. No antiviral therapeutic agent has demonstrated improved outcome in controlled clinical trials. Pleconaril, an inhibitor of enterovirus replication, was tested in two placebo-controlled clinical trials. Of 607 randomized patients in a multicenter, double-blind placebo-controlled study of pleconaril (200 mg three times daily versus an identical-appearing placebo), 240 patients were confirmed to have enterovirus infection. The time to headache resolution was evaluated by using Kaplan-Meier survival methodology. A Cox regression model evaluated multivariate factors associated with disease resolution. Resolution of headache in patients with concomitant moderate to severe nausea at baseline occurred at a median of 9.5 days in the absence of therapy and was reduced to 7.0 days for pleconaril recipients (P = 0.009). For a headache score of >5 alone, treated patients resolved headache significantly more rapidly (P = 0.005). Males resolved headache 50% faster than females. Regardless of randomization group, patients with a baseline headache score of 5 or greater resolved headache 50% more slowly than patients with a baseline headache score of 4. No differences in either clinical or laboratory adverse events were noted. Over 50% of untreated patients had a persistent headache that was greater than 1 week in duration. Pleconaril shortened the course of illness compared to placebo recipients, especially in the early disease course. However, the benefit was achieved only modestly in a subgroup analysis of patients with more severe disease after adjusting for confounding variables.

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Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01751-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Peter Witters ◽

Andrew C. Edmondson ◽

Christina Lam ◽

Christin Johnsen ◽

Marc C. Patterson ◽

...

Keyword(s):

Clinical Trials ◽

Natural History ◽

Randomized Study ◽

Short Term ◽

Double Blind ◽

Natural History Study ◽

Natural History Studies ◽

Carbohydrate Deficient Transferrin ◽

Spontaneous Improvement

AbstractA recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study’s conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin. We have likewise observed improvements in transferrin glycosylation without mannose supplementation. This observation questions the reliability of transferrin as a therapeutic outcome measure in clinical trials for PMM2-CDG. We are concerned that renewed focus on mannose therapy in PMM2-CDG will detract from clinical trials of more promising therapies. Approaches to increase efficiency of clinical trials and ultimately improve patients’ lives requires prospective natural history studies and identification of reliable biomarkers linked to clinical outcomes in CDG. Collaborations with patients and families are essential to identifying meaningful study outcomes.

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Cardiovascular and cerebrovascular events among patients receiving omalizumab: Pooled analysis of patient-level data from 25 randomized, double-blind, placebo-controlled clinical trials

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2016.12.953 ◽

2017 ◽

Vol 139 (5) ◽

pp. 1678-1680 ◽

Cited By ~ 11

Author(s):

Carlos Iribarren ◽

Kenneth J. Rothman ◽

Mary S. Bradley ◽

Gillis Carrigan ◽

Mark D. Eisner ◽

...

Keyword(s):

Clinical Trials ◽

Pooled Analysis ◽

Controlled Clinical Trials ◽

Double Blind ◽

Double Blind Placebo ◽

Patient Level Data ◽

Patient Level ◽

Cerebrovascular Events ◽

Level Data

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Modafinil Augmentation for Residual Symptoms of Fatigue in Patients with a Partial Response to Antidepressants

Annals of Pharmacotherapy ◽

10.1345/aph.1h526 ◽

2007 ◽

Vol 41 (6) ◽

pp. 1005-1012 ◽

Cited By ~ 18

Author(s):

Jenny Y Lam ◽

Maisha Kelly Freeman ◽

Marshall E Cates

Keyword(s):

Clinical Trials ◽

Data Extraction ◽

Controlled Clinical Trials ◽

Open Label ◽

Double Blind ◽

Residual Symptoms ◽

Randomized Controlled ◽

Manual Search ◽

Number Of Patients ◽

Residual Fatigue

OBJECTIVE: To evaluate the literature discussing the use of modafinil in the treatment of residual symptoms of fatigue in patients with depression. DATA SOURCES: PubMed (1966–March 2007) and International Pharmaceutical Abstracts(1970–March 2007) were searched using the key words modafinil and depression. A manual search of the reference section of the articles retrieved was conducted to identify articles not indexed in either of these sources. STUDY SELECTION AND DATA EXTRACTION: All articles published in English were evaluated. Studies were included if modafinil was used to treat patients with residual fatigue from depression and the effects were measured with validated fatigue subscales. DATA SYNTHESIS: One retrospective study, 5 open-label trials, and 2 randomized controlled clinical trials met the inclusion criteria for assessment of residual symptoms of fatigue as assessed by commonly used fatigue subscales after modafinil administration. Although improvement with fatigue has occurred with modafinil therapy, literature regarding the topic is limited by the lack of well-controlled clinical trials. Modafinil does appear to improve residual fatigue with depression as evidenced by open-label trials; however, the efficacy of this agent has not been duplicated in randomized controlled trials. The open-label trials that have been conducted often had no comparator and a small number of patients. In addition, outcome measures used in the studies were not consistent between trials. Modafinil appears to be well tolerated, with the main adverse effects being headache and nausea. CONCLUSIONS: Open-label trials indicate that modafinil may be effective in ameliorating fatigue associated with depression; however, this effect has not been reproduced in randomized, double-blind, placebo-controlled clinical trials. Therefore, the use of modafinil for the treatment of residual fatigue is not recommended due to the lack of reproducible data of its efficacy. Long-term, adequately powered clinical trials should be conducted to determine its place in therapy.

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Homeopathic aggravations: a systematic review of randomised, placebo-controlled clinical trials

Homeopathy ◽

10.1016/s1475-4916-03-00007-9 ◽

2003 ◽

Vol 92 (02) ◽

pp. 92-98

Author(s):

S Grabia ◽

E Ernst

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Effects ◽

Randomised Clinical Trials ◽

Controlled Clinical Trials ◽

Double Blind ◽

Literature Searches

AbstractHomeopathic aggravations have often been described anecdotally. However, few attempts have been made to scientifically verify their existence. This systematic review aimed at comparing the frequency of homeopathic aggravations in the placebo and verum groups of double-blind, randomised clinical trials. Eight independent literature searches were carried out to identify all such trials mentioning either adverse effects or aggravations. All studies thus found were validated and data were extracted by both authors. Twenty-four trials could be included. The average number of aggravations was low. In total, 50 aggravations were attributed to patients treated with placebo and 63 to patients treated with homoeopathically diluted remedies. We conclude that this systematic review does not provide clear evidence that the phenomenon of homeopathic aggravations exists.

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