RESUMO
First popularized almost a century ago in epidemiologic research by Ronald Fisher and Jerzy Neyman, the P-value has become perhaps the most misunderstood and even misused statistical value or descriptor. Indeed, modern clinical research has now come to be centered around and guided by an arbitrary P-value of <0.05 as a magical threshold for significance, so much so that experimental design, reporting of experimental findings, and interpretation and adoption of such findings have become largely dependent on this "significant" P-value. This has given rise to multiple biases in the overall body of biomedical literature that threatens the very validity of clinical research. Ultimately, a drive toward reporting a "significant" P-value (by various statistical manipulations) risks creating a falsely positive body of science, leading to (i) wasted resources in pursuing fruitless research and (ii) futile or even harmful policies/therapeutic recommendations. This article reviews the history of the P-value, the conceptual basis of P-value in the context of hypothesis testing and challenges in critically appraising clinical evidence vis-à-vis the P-value. This review is aimed at raising awareness of the pitfalls of this rigid observation of the threshold of statistical significance when evaluating clinical trials and to generate discussion regarding whether the scientific body needs a rethink about how we decide clinical significance.
Assuntos
Medicina Baseada em Evidências , Humanos , Pesquisa Biomédica , Projetos de Pesquisa , Interpretação Estatística de DadosRESUMO
OBJECTIVE: Motor Unit Number Index (MUNIX) is a quantitative neurophysiological method that reflects loss of motor neurons in Amyotrophic Lateral Sclerosis (ALS) in longitudinal studies. It has been utilized in one natural history ALS study and one drug trial (Biogen USA) after training and qualification of raters. METHODS: Prior to testing patients, evaluators had to submit test-retest data of 4 healthy volunteers. Twenty-seven centres with 36 raters measured MUNIX in 4 sets of 6 different muscles twice. Coefficient of variation of all measurements had to be <20% to pass the qualification process. MUNIX COV of the first attempt, number of repeated measurements and muscle specific COV were evaluated. RESULTS: COV varied considerably between raters. Mean COV of all raters at the first measurements was 12.9%⯱â¯13.5 (median 8.7%). Need of repetitions ranged from 0 to 43 (mean 10.7⯱â¯9.1, median 8). Biceps and first dorsal interosseus muscles showed highest repetition rates. MUNIX variability correlated considerably with variability of compound muscle action potential. CONCLUSION: MUNIX revealed generally good reliability, but was rater dependent and ongoing support for raters was needed. SIGNIFICANCE: MUNIX can be implemented in large clinical trials as an outcome measure after training and a qualification process.
Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/fisiopatologia , Recrutamento Neurofisiológico/fisiologia , Esclerose Lateral Amiotrófica/epidemiologia , Feminino , Humanos , Estudos Longitudinais , MasculinoRESUMO
The presence of P/Q type voltage gated calcium channel (VGCC) antibodies has been strongly correlated with Lambert Eaton Syndrome (LES), present in 90% of non-immunocompromised patients with LES. However, there have been case reports which have shown its association between paraneoplastic syndrome affecting both central nervous system and the peripheral nervous system causing encephalomyelitis and sensory neuronopathy/neuropathy. We present a case of a young man, who presented with encephalomyelitis, and was further noted to have superimposed cervical polyradiculopathy associated with P/Q type VGCC antibodies.
Assuntos
Autoanticorpos/imunologia , Canais de Cálcio Tipo P/imunologia , Canais de Cálcio Tipo Q/imunologia , Encefalomielite/imunologia , Polirradiculopatia/imunologia , Autoanticorpos/sangue , Encefalomielite/complicações , Humanos , Masculino , Polirradiculopatia/complicações , Adulto JovemRESUMO
Complex interactions between pain, depression, and anxiety impact quality of life in patients with ALS. Psychological approaches to pain control may be useful. This study explored the role of self-efficacy in mitigating pain. Individuals registered with the Agency for Toxic Substances and Disease Registry National ALS Registry and who experienced pain were invited to participate in an online survey. Subjects completed the Brief Pain Inventory-Short Form, Hospital Anxiety and Depression Scale, and Chronic Pain Self-Efficacy Scale. Correlations between variables were determined. Multiple linear regression models assessed relationships between depression, anxiety and self-efficacy predictions, and pain severity, interference, and relief. Results recorded that there were 197 participants (58% males, mean age 59 ± 10 years). Cases or borderline cases of depression or anxiety were common. Mean levels of pain were moderate. Higher pain self-efficacy scores predicted lower pain severity, lower pain interference, and higher pain relief with treatment. As depression scores increased, pain interference with daily life was higher. In conclusion, anxiety and depression are common in patients with ALS and pain. Self-efficacy appears to mitigate pain. A multifactorial approach to pain management should be considered in these patients, addressing mental health and self-efficacy to augment pharmacologic pain treatments.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/psicologia , Dor/etiologia , Transtornos Psicóticos/etiologia , Autoeficácia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/psicologia , Manejo da Dor , Medição da Dor , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Análise de RegressãoRESUMO
This study was undertaken to determine which symptoms are perceived to be most problematic for patients with ALS and how their severity changes over time. A retrospective study was performed of data from a randomized, double-blind, placebo-controlled trial of ceftriaxone in ALS. Participants completed the ALS Specific Quality of Life Instrument (ALSSQoL) at baseline and at intervals up to 96 weeks. Ten ALSSQoL items ask participants to rate how problematic symptoms are (the subjective feeling of burden of these symptoms), ranging from 0 (no problem) to 10 (tremendous problem). Six are non-bulbar (pain, fatigue, breathing, strength and ability to move, sleep, and bowel and bladder) and four are bulbar (eating, speaking, excessive saliva, and mucus). Results revealed that there were 82 subjects (56% males, mean age 53 ± 10.3 years) with ALSSQoL data for weeks 0 and 96. All 10 symptoms became more problematic over time. For non-bulbar symptoms, strength/ability to move and fatigue were the most problematic. Speaking was the most problematic bulbar symptom. In conclusion, although all the symptoms in the ALSSQoL were acknowledged as problematic, some had greater impact than others. All became more problematic over time. This should help prioritize research into symptom management, and assist individual clinicians in their approach to patient care.
Assuntos
Esclerose Lateral Amiotrófica , Paralisia Bulbar Progressiva/etiologia , Gerenciamento Clínico , Adulto , Idoso , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/psicologia , Esclerose Lateral Amiotrófica/terapia , Método Duplo-Cego , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
Our objective was to better understand the experience and impact of pain on ALS patients in the U.S., and to survey ALS physicians on their pain assessment and management practices. Individuals with ALS were invited to complete an online survey of pain in ALS. ALS specialist physicians were sent an e-mail survey about their experiences in evaluating and managing patients' pain. Nearly 75% of patients with ALS reported significant pain, and most thought that ALS was the source of at least some of this pain. Pain intensity scores (mean 3.9/10) and pain interference scores (mean 4.3/10) were moderate on average, but nearly 80% of participants were using pain medication, including 22% using opioids. Nearly 25% of patients thought they needed stronger pain medication than they were receiving. Physicians generally assess and manage pain in ALS patients, but few use standardized assessment tools. Nearly two-thirds felt that there is a need for better pain management practices and more than one-third felt better training was needed. In conclusion, pain in patients with ALS is not always well controlled. Improvement in care may be facilitated by a more standardized approach to evaluation, and by additional education and training of ALS health care professionals.
Assuntos
Esclerose Lateral Amiotrófica/epidemiologia , Atitude do Pessoal de Saúde , Manejo da Dor/estatística & dados numéricos , Medição da Dor/estatística & dados numéricos , Dor/epidemiologia , Satisfação do Paciente/estatística & dados numéricos , Atividades Cotidianas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos , Medição da Dor/métodos , Padrões de Prática Médica/estatística & dados numéricos , Prevalência , Qualidade de Vida , Fatores de Risco , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.
RESUMO
Anti-MAG neuropathy is a very rare form of acquired polyneuropathy associated with IgM monoclonal gammopathy of undetermined significance (MGUS). We conducted a retrospective review of 194 consecutive MGUS patients seen at the Penn State Hershey Cancer Institute. We identified six patients among 37 (16 %) with IgM MGUS with anti-MAG neuropathy. Interestingly, an additional patient had anti-MAG neuropathy without MGUS. Common clinical manifestations were numbness and paresthesias of the extremities and gait imbalance. All four patients treated with rituximab and none of the three untreated ones had a subjective improvement of their symptoms. We conclude that all patients with IgM MGUS and neuropathy should be screened for anti-MAG antibodies and, if positive, they should be offered treatment with rituximab.
Assuntos
Anticorpos Anti-Idiotípicos/sangue , Imunoglobulina M/sangue , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Polineuropatias/sangue , Polineuropatias/diagnóstico , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The paraproteinemias are a heterogeneous group of disorders in which monoclonal plasma cells cause the proliferation of monoclonal proteins. They are of importance to clinicians because they often occur in association with neuropathies. Neurologists play a particularly important role when the neuropathy is the presenting feature, in which case they may uncover clinical, laboratory, radiologic, electrodiagnostic, or biopsy findings that lead to identification of the underlying paraproteinemia. The frequency of neuropathies in these patients, and the extent to which such neuropathies dominate the clinical picture, varies significantly between the different paraproteinemias. Treatments may be aimed specifically at the neuropathy, or against the underlying hematologic disorder. In all patients with paraproteinemias, the neurologist can work collaboratively with the hematologist to formulate therapeutic plans and goals and can provide follow-up and monitoring to determine the response of the neuropathy to treatment.