The concept of the minimal clinically important difference (MCID) emerged from the recognition that statistical significance alone is not enough to determine the clinical relevance of treatment ...effects in clinical research. In many cases, statistically significant changes in outcomes may not be meaningful to patients or may not result in any tangible improvements in their health. This has led to a growing emphasis on the importance of measuring patient-reported outcome measures (PROMs) in clinical trials and other research studies, in order to capture the patient perspective on treatment effectiveness. MCID is defined as the smallest change in scores that is considered meaningful or important to patients. MCID is particularly important in fields such as neurology, where many of the outcomes of interest are subjective or based on patient-reported symptoms. This review discusses the challenges associated with interpreting outcomes of clinical trials based solely on statistical significance, highlighting the importance of considering clinical relevance and patient perception of change. There are two main approaches to estimating MCID: anchor-based and distribution-based. Anchor-based approaches compare change scores using an external anchor, while distribution-based approaches estimate MCID values based on statistical characteristics of scores within a sample. MCID is dynamic and context-specific, and there is no single 'gold standard' method for estimating it. A range of MCID thresholds should be defined using multiple methods for a disease under targeted intervention, rather than relying on a single absolute value. The use of MCID thresholds can be an important tool for researchers, neurophysicians and patients in evaluating the effectiveness of treatments and interventions, and in making informed decisions about care.
Neurosarcoidosis: The pan-neurology disease Agarwal, Ayush; Garg, Divyani; Garg, Ajay ...
Annals of the Indian Academy of Neurology,
07/2023, Letnik:
26, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Neurosarcoidosis (NS) is a protean illness with multiple clinical and radiological presentations giving it the moniker of "a chameleon" or the great mimic. NS can present as a wide spectrum of ...neurological syndromes localizing both to the central and peripheral nervous systems. The absence of a diagnostic serum test makes it difficult to diagnose with certainty and remains largely a histopathological diagnosis and one of exclusion. A high index of suspicion should be there in suspecting NS, and it should always be excluded among patients presenting with acute to subacute neurological deficits.
Minimum clinically important difference (MCID) is the smallest change in an outcome measure that is considered clinically meaningful. Using validated MCID thresholds for outcomes powers trials ...adequately to detect meaningful treatment effects, aids in their interpretation and guides development of new outcome measures.
To provide a comprehensive summary of MCID thresholds of various symptom severity scales reported in movement disorder.
We conducted systematic review of the literature and included studies of one or more movement disorders, and reporting MCID scales.
2763 reports were screened. Final review included 32 studies. Risk of bias (RoB) assessment showed most studies were of good quality. Most commonly evaluated scale was Unified Parkinson's Disease Rating Scale (UPDRS) (11 out of 32). Four studies assessing MDS-UPDRS had assessed its different sub-parts, reporting a change of 2.64,3.05,3.25 and 0.9 points to detect clinically meaningful improvement and 2.45,2.51,4.63 and 0.8 points to detect clinically meaningful worsening, for the Part I, II, III and IV, respectively. For Parts II + III, I + II + III and I + II + III + IV, MCID thresholds reported for clinically meaningful improvement were 5.73, 4.9, 6.7 and 7.1 points respectively; while those for clinically meaningful worsening were 4.7, 4.2, 5.2 and 6.3 points, respectively. MCID thresholds reported for other scales included Abnormal Involuntary Movement Scale (AIMS), Toronto Western Spasmodic Torticollis Rating Scale (TWSRS), and Burke-Fahn-Marsden Dystonia Scale (BFMD).
This review summarizes all the MCID thresholds currently reported in Movement disorders research and provides a comprehensive resource for future trials, highlighting the need for standardized and validated MCID scales in movement disorder research.
Background
Bacopa monnieri, a herb that has been used for many centuries in India, has shown neuroprotective effects in animal and in vitro studies; human studies on patients with Alzheimer disease ...have been inconclusive.
Objective
The primary objective of this review was to determine the clinical efficacy and safety of B. monnieri in persons with mild, moderate, or severe dementia, or mild cognitive impairment, due to Alzheimer disease.
Methods
We searched PubMed, Embase, Cochrane Library, clinical trial registries (World Health Organization, Australia-New Zealand, United States, and South Africa), the metaRegister of Controlled Trials, and CINAHL. We intended to include all randomized and quasi-randomized controlled trials that compared B. monnieri, its extract or active ingredients (at any dosage), with a placebo or a cholinesterase inhibitor among adults with dementia due to Alzheimer disease and in those with mild cognitive impairment due to Alzheimer disease.
Results
Our comprehensive search yielded 5 eligible studies. A total of 3 studies used B. monnieri in combination with herbal extracts while the remaining 2 used B. monnieri extracts only. Two studies compared B. monnieri with donepezil while the others used a placebo as the control. There was considerable variation in the B. monnieri dose used (ranging between 125 mg to 500 mg twice daily) and heterogeneity in treatment duration, follow-up, and outcomes. The major outcomes were Mini-Mental State Examination scores reported in 3 trials, Cognitive subscale scores of the Alzheimer’s Disease Assessment Scale in 1 study, and a battery of cognitive tests in 2 studies. Using the Cochrane risk-of-bias tool, overall, we judged all 5 studies to be at high risk of bias. While all studies reported a statistically significant difference between B. monnieri and the comparator in at least one outcome, we rated the overall quality of evidence for the Alzheimer’s Disease Assessment Scale-Cognitive Subscale, Postgraduate Institute Memory Scale, Mini-Mental State Examination, and Wechsler Memory Scale to be very low due to downgrading by 2 levels for high risk of bias and 1 more level for impreciseness due to small sample sizes and wide CIs.
Conclusions
There was no difference between B. monnieri and the placebo or donepezil in the treatment of Alzheimer disease based on very low certainty evidence. No major safety issues were reported in the included trials. Future randomized controlled trials should aim to recruit more participants and report clinically meaningful outcomes.
Trial Registration
PROSPERO CRD42020169421; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=169421
Ifosfamide, an analog of cyclophosphamide, is commonly used as a chemotherapeutic agent to treat sarcomas and solid tumors. However, neurotoxicity is a rare side effect of this drug. When present, ...the symptoms range from confusion, agitation, and delirium in mild cases to mutism, visual blurring, hallucinations, seizures, stupor, and even coma in extreme cases. Within this spectrum, extrapyramidal symptoms are extremely rare, and when present, may not revert with drug discontinuation. Sequelae may occasionally persist even after discontinuation of the drug. Our case illustrates a rare occurrence of ifosfamide-induced extrapyramidal neurotoxicity in a patient with metastatic phyllodes tumor of the breast and concomitant COVID-19 illness. Ifosfamide-induced extrapyramidal neurotoxicity is a clinical diagnosis of exclusion and requires ruling out of other possible causes. The diagnosis is supported by a temporal correlation with drug administration, presence of risk factors, and improvement after infusion cessation, along with normal brain imaging.
Disease modification trials in dementia and mild cognitive impairment (MCI) have not met with success. One potential criticism of these trials is the lack of sensitive outcome measures. A large ...number of outcome measures have been employed in dementia and MCI trials. This review aims to describe and analyze the utility of cognitive/clinical outcome measures in Alzheimer’s disease (AD) and MCI trials. Methods: A PubMed search was conducted using relevant MeSH terms and exploded keywords. The search was confined to English language publications of human studies from the last five years which describe the latest trends in the use of outcome measures. Results: Despite broad use, the outcome measures employed are heterogeneous, with little data on correlations between scales. Another problem is that most studies are over-reliant on clinician/researcher assessment and cognitive outcomes, and there is a definite lack of stakeholder input. Finetuning of the paradigm is also required for people with early-stage disease, mild to moderate disease, and advanced dementia, as the outcome measures in these subgroups have varying relevance. Disease modification/prevention is an appropriate goal in early disease, whereas palliation and freedom from discomfort are paramount in later stages. The outcome measures selected must be suitable for and sensitive to these particular care goals. Although there is a shift to enrich MCI cohorts using a biomarker-based approach, the clinical relevance of such outcome measures remains uncertain. Conclusions: Outcome measures in dementia/MCI trials remain inhomogeneous and diverse, despite extensive use. Outcome measures fall within several paradigms, including cognitive, functional, quality-of-life, biomarker-based, and patient-reported outcome measures. The success of future disease-modifying trials is reliant to a large extent on the selection of outcome measures which combine all outcomes of clinical relevance as well as clinical meaning. Outcome measures should be tied to the type and stage of dementia and to the specific interventions employed.
Background: Recent respiratory infection including SARS-CoV-2 is an independent risk factor for acute cerebrovascular disease. Purpose: There have been reports linking haemorrhagic strokes to ...SARS-CoV-2 infection during this pandemic, which lead us to evaluate if SARS-CoV-2 infection could be associated with increased risk of intracerebral haemorrhage (ICH). Methods: A retrospective observational study evaluating all stroke cases admitted in our centre in the past one month. Results: More than half (56%) had ICH, compared to 22% last year. Two patients with ICH were SARS-CoV-2 positive and they had no or mild respiratory symptoms and had higher occurrence of renal dysfunction. Conclusion: There could be possible association between ICH and SARS-CoV-2 infections. However, a prospective study with larger sample size is needed to elucidate the pathogenesis.
Chronic inflammation is central to the pathogenesis of many chronic inflammatory conditions. This review aims to analyze whether the practice of yoga, or yogic meditation and breathing, has any ...effect on the levels of inflammatory cytokines and other inflammatory markers in patients with various chronic inflammatory diseases such as rheumatoid arthritis, neoplastic disorders, and asthma, as well as in healthy subjects, compared to usual care or sham interventions. A comprehensive search of databases (PubMed, CENTRAL, Embase, and CINAHL) was performed. Randomized controlled trials (RCTs) that evaluated the effects of yoga as an intervention on inflammatory markers were analyzed. A total of 26 studies were included. Only two studies had a low risk of bias (RoB); 24 other studies had a high RoB. Most studies (n=24) reported a favorable outcome with yoga, irrespective of the type of yoga used, the condition studied, and the duration of the intervention. The commonly reported inflammatory markers included IL-6 (n=17), tumor necrosis factor-alpha
(TNF-a) (n=13), and C-reactive protein (CRP) (n=10). Most studies showed a significant reduction in inflammatory markers in the yoga group (YG) compared to the control group (CG). Few studies also showed significant improvement in markers of cellular immunity (interferon gamma (IFN-g), IL-10, and transforming growth factor-beta (TGF-b); n=2 each) and improved mucosal defense (IgA, IL-6, and IL-2; n=2 each). A meta-analysis of IL-6, TNF-a, and CRP showed yoga had a favorable effect on the levels of these markers, but it was not statistically significant. Current evidence suggests that yoga can be a complementary intervention for various chronic inflammatory conditions. However, the quality of the evidence is poor, along with considerable heterogeneity. In the future, investigators should describe the intervention better, with a uniform assortment of outcome measures and treatment conditions, to generate high-quality evidence.
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