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Systematic Reviews Mar 2023Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo treatments in terms of their efficacy and safety in patients with PDPN.
METHODS
Following the PRISMA guidelines, we searched the Cochrane Library, PubMed, and Embase databases for relevant English articles published before January 11, 2021. Treatment efficacy and safety were assessed in terms of pain improvement, patient-reported health-related performance, and patients' quality of life.
RESULTS
We reviewed a total of 7 randomized controlled trials. Regarding pain improvement, duloxetine was more efficacious than placebo (mean difference [MD] - 0.89; 95% confidence interval [CI] - 1.09 to - 0.69; P < .00001). Furthermore, duloxetine significantly improved the patients' quality of life, which was assessed using the Clinical Global Impression severity subscale (MD - 0.48; 95% CI - 0.61 to - 0.36; P < .00001), Patient Global Impression of Improvement scale (MD - 0.50; 95% CI - 0.64 to - 0.37; P < .00001), and European Quality of Life Instrument 5D version (MD 0.04; 95% CI 0.02 to 0.07; P = .0002). Severe adverse events were rare, whereas nausea, somnolence, dizziness, fatigue, constipation, and decreased appetite were common; approximately, 12.6% of all patients dropped out because of the common symptoms.
CONCLUSIONS
Duloxetine is more efficacious than placebo treatments in patients with PDPN. The rarity of severe adverse events indicates that duloxetine is safe. When a 60-mg dose is insufficient, 120 mg of duloxetine may improve PDPN symptoms. Our findings may help devise optimal treatment strategies for PDPN.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021225451.
Topics: Humans; Duloxetine Hydrochloride; Diabetic Neuropathies; Quality of Life; Randomized Controlled Trials as Topic; Pain; Diabetes Mellitus
PubMed: 36945033
DOI: 10.1186/s13643-023-02185-6 -
The Canadian Journal of Neurological... Jan 2021Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological manifestations and complications in COVID-19.
METHODS
We conducted a systematic review and meta-analysis that included cohort and case series/reports involving a population of patients confirmed with COVID-19 infection and their neurologic manifestations. We searched the following electronic databases until April 18, 2020: PubMed, Embase, Scopus, and World Health Organization database (PROSPERO registration number: CRD42020180658).
RESULTS
From 403 articles identified, 49 studies involving a total of 6,335 confirmed COVID-19 cases were included. The random-effects modeling analysis for each neurological symptom showed the following proportional point estimates with 95% confidence intervals: "headache" (0.12; 0.10-0.14; I2 = 77%), "dizziness" (0.08; 0.05-0.12; I2 = 82%), "headache and dizziness" (0.09; 0.06-0.13; I2 = 0%), "nausea" (0.07; 0.04-0.11; I2 = 79%), "vomiting" (0.05; 0.03-0.08; I2 = 74%), "nausea and vomiting" (0.06; 0.03-0.11; I2 = 83%), "confusion" (0.05; 0.02-0.14; I2 = 86%), and "myalgia" (0.21; 0.18-0.25; I2 = 85%). The most common neurological complication associated with COVID-19 infection was vascular disorders (n = 23); other associated conditions were encephalopathy (n = 3), encephalitis (n = 1), oculomotor nerve palsy (n = 1), isolated sudden-onset anosmia (n = 1), Guillain-Barré syndrome (n = 1), and Miller-Fisher syndrome (n = 2). Most patients with neurological complications survived (n = 14); a considerable number of patients died (n = 7); and the rest had unclear outcomes (n = 12).
CONCLUSION
This review revealed that neurologic involvement may manifest in COVID-19 infection. What has initially been thought of as a primarily respiratory illness has evolved into a wide-ranging multi-organ disease.
Topics: Anosmia; Brain Diseases; COVID-19; Cerebral Hemorrhage; Cerebral Infarction; Cerebrovascular Disorders; Confusion; Dizziness; Encephalitis; Guillain-Barre Syndrome; Headache; Humans; Myalgia; Nausea; Oculomotor Nerve Diseases; SARS-CoV-2; Sinus Thrombosis, Intracranial; Vomiting
PubMed: 32665054
DOI: 10.1017/cjn.2020.146 -
Pain and Therapy Jun 2021Peripheral neuropathic pain (PNP) arises either acutely or in the chronic phase of a lesion or disease of the peripheral nervous system and is associated with a notable... (Review)
Review
INTRODUCTION
Peripheral neuropathic pain (PNP) arises either acutely or in the chronic phase of a lesion or disease of the peripheral nervous system and is associated with a notable disease burden. The management of PNP is often challenging. The aim of this systematic review was to evaluate current evidence, derived from randomized controlled trials (RCTs) that have assessed pharmacological interventions for the treatment of PNP due to polyneuropathy (PN).
METHODS
A systematic search of the PubMed database led to the identification of 538 papers, of which 457 were excluded due to not meeting the eligibility criteria, and two articles were identified through screening of the reference lists of the 81 eligible studies. Ultimately, 83 papers were included in this systematic review.
RESULTS
The best available evidence for the management of painful diabetic polyneuropathy (DPN) is for amitriptyline, duloxetine, gabapentin, pregabalin and venlafaxine as monotherapies and oxycodone as add-on therapy (level II of evidence). Tramadol appears to be effective when used as a monotherapy and add-on therapy in patients with PN of various etiologies (level II of evidence). Weaker evidence (level III) is available on the effectiveness of several other agents discussed in this review for the management of PNP due to PN.
DISCUSSION
Response to treatment may be affected by the underlying pathophysiological mechanisms that are involved in the pathogenesis of the PN and, therefore, it is very important to thoroughly investigate patients presenting with PNP to determine the causes of this neuropathy. Future RCTs should be conducted to shed more light on the use of pharmacological approaches in patients with other forms of PNP and to design specific treatment algorithms.
PubMed: 33145709
DOI: 10.1007/s40122-020-00210-3 -
Pain as a First Manifestation of Paraneoplastic Neuropathies: A Systematic Review and Meta-Analysis.Pain and Therapy Dec 2017Paraneoplastic neurological syndromes (PNS) consist of a heterogeneous group of neurological disorders triggered by cancer. The aim of this systematic review is to... (Review)
Review
INTRODUCTION
Paraneoplastic neurological syndromes (PNS) consist of a heterogeneous group of neurological disorders triggered by cancer. The aim of this systematic review is to estimate the reported prevalence of pain in patients with paraneoplastic peripheral neuropathy (PPN).
METHODS
A systematic computer-based literature search was conducted on PubMed database.
RESULTS
Our search strategy resulted in the identification of 126 articles. After the eligibility assessment, 45 papers met the inclusion criteria. Full clinical and neurophysiological data were further extracted and involved 92 patients with PPN (54.5% males, mean age 60.0 ± 12.2 years). The commonest first manifestation of PPN is sensory loss (67.4%), followed by pain (41.3%), weakness (22.8%), and sensory ataxia (20.7%). In 13.0% of the cases, pain was the sole first manifestation of the PPN. During the course of the PPN, 57.6% of the patients may experience pain secondary to the neuropathy.
CONCLUSIONS
Pain is very prevalent within PPN. Pain specialists should be aware of this. Detailed history-taking, full clinical examination, and requesting nerve conduction studies might lead to an earlier diagnosis of an underlying malignancy.
PubMed: 28669085
DOI: 10.1007/s40122-017-0076-3 -
Acta Diabetologica Jan 2022Diabetic neuropathy is among the most frequent complications of both type 1 (T1DM) and type 2 diabetes (T2DM) and commonly manifests as a distal symmetrical... (Review)
Review
Diabetic neuropathy is among the most frequent complications of both type 1 (T1DM) and type 2 diabetes (T2DM) and commonly manifests as a distal symmetrical polyneuropathy (DSPN). Despite evidence that T1DM- and T2DM-related DSPN are separate entities, most of our knowledge on diabetic DSPN derives from studies focused on type 2 diabetes. This systematic review provides an overview of current evidence on DSPN in T1DM, including its epidemiological, pathophysiological and clinical features, along with principal diagnostic tests findings. This review included 182 clinical and preclinical studies. The results indicate that DSPN is a less frequent complication in T1DM compared with T2DM and that distinctive pathophysiological mechanisms underlie T1DM-related DSPN development, with hyperglycemia as a major determinant. T1DM-related DSPN more frequently manifests with non-painful than painful symptoms, with lower neuropathic pain prevalence compared with T2DM-associated DSPN. The overt clinical picture seems characterized by a higher prevalence of large fiber-related clinical signs (e.g., ankle reflexes reduction and vibration hypoesthesia) and to a lesser extent small fiber damage (e.g., thermal or pinprick hypoesthesia). These findings as a whole suggest that large fibers impairment plays a dominant role in the clinical picture of symptomatic T1DM-related DSPN. Nevertheless, small fiber diagnostic testing shows high diagnostic accuracy in detecting early nerve damage and may be an appropriate diagnostic tool for disease monitoring and screening.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Polyneuropathies; Vibration
PubMed: 34213655
DOI: 10.1007/s00592-021-01767-x -
The Cochrane Database of Systematic... Dec 2014Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy. A variety of interventions for subjective fatigue are available, but little is known about their efficacy or the likelihood of any adverse effects for people with peripheral neuropathy.
OBJECTIVES
To assess the effects of drugs and physical, psychological or behavioural interventions for fatigue in adults or children with peripheral neuropathy.
SEARCH METHODS
On 5 November 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, LILACS and AMED. We also searched reference lists of all studies identified for inclusion and relevant reviews, and contacted the authors of included studies and known experts in the field to identify additional published or unpublished data. We also searched trials registries for ongoing studies.
SELECTION CRITERIA
We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs comparing any form of intervention for fatigue management in adults with peripheral neuropathy with placebo, no intervention or an alternative form of intervention for fatigue. Interventions considered included drugs, pacing and grading of physical activity, general or specific exercise, compensatory strategies such as orthotics, relaxation, counselling, cognitive and educational strategies.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed risk of bias and extracted study data. We contacted study authors for additional information. We collected information on adverse events from the included trials.
MAIN RESULTS
The review includes three trials, which were all at low risk of bias, involving 530 people with peripheral neuropathy. The effects of amantadine from one randomised, double-blind, placebo-controlled, cross-over trial comparing amantadine with placebo for the treatment of fatigue in 80 people with Guillain-Barré syndrome (GBS) were uncertain for the proportion of people achieving a favourable outcome six weeks post-intervention (odds ratio (OR) 0.56 (95% confidence interval (CI) 0.22 to 1.35, N = 74, P = 0.16). We assessed the quality of this evidence as low. Two parallel-group randomised double-blind, placebo-controlled trials comparing the effects of two doses of ascorbic acid with placebo for reducing fatigue in adults with Charcot-Marie-Tooth disease type 1A (CMT1A) showed that the effects of ascorbic acid at either dose are probably small (standardised mean difference (SMD) -0.12 (95% CI -0.32 to 0.08, n = 404, P = 0.25)) for change in fatigue after 12 to 24 months (moderate quality evidence). Neither ascorbic acid study measured fatigue at four to 12 weeks, which was our primary outcome measure. No serious adverse events were reported with amantadine. Serious adverse events were reported in the trials of ascorbic acid. However,risk of serious adverse events was similar with ascorbic acid and placebo.
AUTHORS' CONCLUSIONS
One small imprecise study in people with GBS showed uncertain effects of amantadine on fatigue. In two studies in people with CMT1A there is moderate-quality evidence that ascorbic acid has little meaningful benefit on fatigue. Information about adverse effects was limited, although both treatments appear to be well tolerated and safe in these conditions.There was no evidence available from RCTs to evaluate the effect of other drugs or other interventions for fatigue in either GBS, CMT1A or other causes of peripheral neuropathy. The cost effectiveness of different interventions should also be considered in future randomised clinical trials.
Topics: Adult; Amantadine; Ascorbic Acid; Charcot-Marie-Tooth Disease; Child; Fatigue; Guillain-Barre Syndrome; Humans; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic
PubMed: 25519471
DOI: 10.1002/14651858.CD008146.pub2 -
Orphanet Journal of Rare Diseases Sep 2020Alström Syndrome (ALMS) is an ultra-rare multisystem genetic disorder caused by autosomal recessive variants in the ALMS1 gene, which is located on chromosome 2p13....
Alström Syndrome (ALMS) is an ultra-rare multisystem genetic disorder caused by autosomal recessive variants in the ALMS1 gene, which is located on chromosome 2p13. ALMS is a multisystem, progressive disease characterised by visual disturbance, hearing impairment, cardiomyopathy, childhood obesity, extreme insulin resistance, accelerated non-alcoholic fatty liver disease (NAFLD), renal dysfunction, respiratory disease, endocrine and urologic disorders. Clinical symptoms first appear in infancy with great variability in age of onset and severity. ALMS has an estimated incidence of 1 case per 1,000,000 live births and ethnically or geographically isolated populations have a higher-than-average frequency. The rarity and complexity of the syndrome and the lack of expertise can lead to delayed diagnosis, misdiagnosis and inadequate care. Multidisciplinary and multiprofessional teams of experts are essential for the management of patients with ALMS, as early diagnosis and intervention can slow the progression of multi-organ dysfunctions and improve patient quality of life.These guidelines are intended to define standard of care for patients suspected or diagnosed with ALMS of any age. All information contained in this document has originated from a systematic review of the literature and the experiences of the authors in their care of patients with ALMS. The Appraisal of Guidelines for Research & Evaluation (AGREE II) system was adopted for the development of the guidelines and for defining the related levels of evidence and strengths of recommendations.These guidelines are addressed to: a) specialist centres, other hospital-based medical teams and staffs involved with the care of ALMS patients, b) family physicians and other primary caregivers and c) patients and their families.
Topics: Alstrom Syndrome; Child; Consensus; Humans; Practice Guidelines as Topic; Quality of Life
PubMed: 32958032
DOI: 10.1186/s13023-020-01468-8 -
Journal of Medical Genetics Dec 2023Alström syndrome (ALMS; #203800) is an ultrarare monogenic recessive disease. This syndrome is associated with variants in the gene, which encodes a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alström syndrome (ALMS; #203800) is an ultrarare monogenic recessive disease. This syndrome is associated with variants in the gene, which encodes a centrosome-associated protein involved in the regulation of several ciliary and extraciliary processes, such as centrosome cohesion, apoptosis, cell cycle control and receptor trafficking. The type of variant associated with ALMS is mostly complete loss-of-function variants (97%) and they are mainly located in exons 8, 10 and 16 of the gene. Other studies in the literature have tried to establish a genotype-phenotype correlation in this syndrome with limited success. The difficulty in recruiting a large cohort in rare diseases is the main barrier to conducting this type of study.
METHODS
In this study we collected all cases of ALMS published to date. We created a database of patients who had a genetic diagnosis and an individualised clinical history. Lastly, we attempted to establish a genotype-phenotype correlation using the truncation site of the patient's longest allele as a grouping criteria.
RESULTS
We collected a total of 357 patients, of whom 227 had complete clinical information, complete genetic diagnosis and meta-information on sex and age. We have seen that there are five variants with high frequency, with p.(Arg2722Ter) being the most common variant, with 28 alleles. No gender differences in disease progression were detected. Finally, truncating variants in exon 10 seem to be correlated with a higher prevalence of liver disorders in patients with ALMS.
CONCLUSION
Pathogenic variants in exon 10 of the gene were associated with a higher prevalence of liver disease. However, the location of the variant in the gene does not have a major impact on the phenotype developed by the patient.
Topics: Humans; Alstrom Syndrome; Cell Cycle Proteins; Phenotype; Exons; Genetic Association Studies
PubMed: 37321834
DOI: 10.1136/jmg-2023-109175 -
The Cochrane Database of Systematic... Jul 2014Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. The efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. The efficacy of levetiracetam for relief of neuropathic pain has not previously been reviewed.
OBJECTIVES
To assess the analgesic efficacy and adverse events of levetiracetam in chronic neuropathic pain conditions in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6) (via the Cochrane Library), MEDLINE, EMBASE, and two clinical trials databases (ClinicalTrials.gov. and the World Health Organisation Clinical Trials Registry Platform) to 3 July 2014, together with reference lists of retrieved papers and reviews.
SELECTION CRITERIA
We included randomised, double-blind studies of two weeks duration or longer, comparing levetiracetam with placebo or another active treatment in adults with chronic neuropathic pain conditions. Studies had to have a minimum of 10 participants per treatments arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction; intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison; 8 to 12 weeks duration; parallel design); second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with at least 200 participants in the comparison; and third tier evidence from data involving fewer than 200 participants that was considered very likely to be biased or used outcomes of limited clinical utility, or both.
MAIN RESULTS
We included six studies: five small, cross-over studies with 174 participants, and one parallel group study with 170 participants. Participants were treated with levetiracetam (2000 mg to 3000 mg daily) or placebo for between four and 14 weeks. Each study included participants with a different type of neuropathic pain; central pain due to multiple sclerosis, pain following spinal cord injury, painful polyneuropathy, central post-stroke pain, postherpetic neuralgia, and post-mastectomy pain.None of the included studies provided first or second tier evidence. The evidence was very low quality, downgraded because of the small size of the treatment arms, and because studies reported results using last observation carried forward (LOCF) imputation for withdrawals or using only participants who completed the study according to the protocol, where there were greater than 10% withdrawals. There were insufficient data for a pooled efficacy analysis in particular neuropathic pain conditions, but individual studies did not show any analgesic effect of levetiracetam compared with placebo. We did pool results for any outcome considered substantial pain relief (≥ 50% pain intensity reduction or 'complete' or 'good' responses on the verbal rating scale) for four studies with dichotomous data; response rates across different types of neuropathic pain was similar with levetiracetam (10%) and placebo (12%), with no statistical difference (risk ratio 0.9; 95% confidence interval (CI) 0.4 to1.7).We pooled data across different conditions for adverse events and withdrawals. Based on very limited data, significantly more participants experienced an adverse event with levetiracetam than with placebo (number needed to treat for an additional harmful event (NNH) 8.0 (95% CI 4.6 to 32)). There were significantly more adverse event withdrawals with levetiracetam (NNH 9.7 (6.7 to 18)).
AUTHORS' CONCLUSIONS
The amount of evidence for levetiracetam in neuropathic pain conditions was very small and potentially biased because of the methods of analysis used in the studies. There was no indication that levetiracetam was effective in reducing neuropathic pain, but it was associated with an increase in participants who experienced adverse events and who withdrew due to adverse events.
Topics: Adult; Analgesics; Chronic Disease; Humans; Levetiracetam; Neuralgia; Piracetam; Randomized Controlled Trials as Topic
PubMed: 25000215
DOI: 10.1002/14651858.CD010943.pub2 -
Clinical Case Reports Jun 2023Guillain-Barré syndrome (GBS) is a rare but possible complication that may occur after COVID-19 vaccination. In this systematic review, we found that GBS presented in...
KEY CLINICAL MESSAGE
Guillain-Barré syndrome (GBS) is a rare but possible complication that may occur after COVID-19 vaccination. In this systematic review, we found that GBS presented in patients with an average age of 58. The average time for symptoms to appear was 14.4 days. Health care providers should be aware of this potential complication.
ABSTRACT
Most instances of Guillain-Barré syndrome (GBS) are caused by immunological stimulation and are discovered after vaccinations for tetanus toxoid, oral polio, and swine influenza. In this systematic study, we investigated at GBS cases that were reported after receiving the COVID-19 vaccination. Based on PRISMA guidelines, we searched five databases (PubMed, Google Scholar, Ovid, Web of Science, and Scopus databases) for studies on COVID-19 vaccination and GBS on August 7, 2021. To conduct our analysis, we divided the GBS variants into two groups, acute inflammatory demyelinating polyneuropathy and non-acute inflammatory demyelinating polyneuropathy (AIDP and non-AIDP), and compared the two groups with mEGOS and other clinical presentation In this systematic review, 29 cases were included in 14 studies. Ten cases belonged to the AIDP variant, 17 were non-AIDP (one case had the MFS variant, one AMAN variant, and 15 cases had the BFP variant), and the two remaining cases were not mentioned. Following COVID-19 vaccination, GBS cases were, on average, 58 years of age. The average time it took for GBS symptoms to appear was 14.4 days. About 56 percent of the cases (56%) were classified as Brighton Level 1 or 2, which defines the highest level of diagnostic certainty for patients with GBS. This systematic review reports 29 cases of GBS following COVID-19 vaccination, particularly those following the AstraZeneca/Oxford vaccine. Further research is needed to assess all COVID-19 vaccines' side effects, including GBS.
PubMed: 37305891
DOI: 10.1002/ccr3.7456