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Journal of the Peripheral Nervous... Sep 2023Several widely used medications, with a relevant efficacy profile, are toxic to the peripheral nervous system and an even larger number of agents are suspected to be... (Review)
Review
BACKGROUND AND AIMS
Several widely used medications, with a relevant efficacy profile, are toxic to the peripheral nervous system and an even larger number of agents are suspected to be neurotoxic. There are concerns about the use of these drugs in patients with Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy. This review provides evidence-based updated recommendations on this clinically relevant topic.
METHODS
A systematic review of the available studies/reports written in English was performed from July to September 2022 including in the search string all reported putative neurotoxic drugs.
RESULTS
The results of our systematic review provide evidence-based support for the statement that use of vincristine, and possibly paclitaxel, can occasionally induce an atypical, and more severe, course of drug-related peripheral neurotoxicity in CMT patients. It is therefore reasonable to recommend caution in the use of these compounds in CMT patients. However, no convincing evidence for a similar recommendation could be found for all other drugs.
INTERPRETATION
It is important that patients with CMT are not denied effective treatments that may prolong life expectancy for cancer or improve their health status if affected by non-oncological diseases. Accurate monitoring of peripheral nerve function in CMT patients treated with any neurotoxic agent remains mandatory to detect the earliest signs of neuropathy worsening and atypical clinical courses. Neurologists monitoring CMT patients as part of their normal care package or for natural history studies should keep detailed records of exposures to neurotoxic medications and support reporting of accelerated neuropathy progression if observed.
Topics: Humans; Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy; Neoplasms; Neurotoxicity Syndromes
PubMed: 37249082
DOI: 10.1111/jns.12566 -
American Journal of Kidney Diseases :... Jan 2022Toxicity from gabapentin and pregabalin overdose is commonly encountered. Treatment is supportive, and the use of extracorporeal treatments (ECTRs) is controversial. The...
Toxicity from gabapentin and pregabalin overdose is commonly encountered. Treatment is supportive, and the use of extracorporeal treatments (ECTRs) is controversial. The EXTRIP workgroup conducted systematic reviews of the literature and summarized findings following published methods. Thirty-three articles (30 patient reports and 3 pharmacokinetic studies) met the inclusion criteria. High gabapentinoid extracorporeal clearance (>150mL/min) and short elimination half-life (<5 hours) were reported with hemodialysis. The workgroup assessed gabapentin and pregabalin as "dialyzable" for patients with decreased kidney function (quality of the evidence grade as A and B, respectively). Limited clinical data were available (24 patients with gabapentin toxicity and 7 with pregabalin toxicity received ECTR). Severe toxicity, mortality, and sequelae were rare in cases receiving ECTR and in historical controls receiving standard care alone. No clear clinical benefit from ECTR could be identified although major knowledge gaps were acknowledged, as well as costs and harms of ECTR. The EXTRIP workgroup suggests against performing ECTR in addition to standard care rather than standard care alone (weak recommendation, very low quality of evidence) for gabapentinoid poisoning in patients with normal kidney function. If decreased kidney function and coma requiring mechanical ventilation are present, the workgroup suggests performing ECTR in addition to standard care (weak recommendation, very low quality of evidence).
Topics: Drug Overdose; Frailty; Gabapentin; Humans; Poisoning; Pregabalin; Renal Dialysis
PubMed: 34799138
DOI: 10.1053/j.ajkd.2021.06.027 -
Journal of Digestive Diseases May 2023Drug-induced liver injury (DILI) is an increasing etiology of liver dysfunction, with various incidence worldwide. To better understand the disease burden and establish... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Drug-induced liver injury (DILI) is an increasing etiology of liver dysfunction, with various incidence worldwide. To better understand the disease burden and establish appropriate preventive and treatment strategies, a systematic review and meta-analysis was conducted.
METHODS
PubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies on the incidence of DILI published up to June 1, 2022. According to the predefined criteria, only population-based studies were included. Incidence was presented as cases per 100 000 person-years with 95% confidence interval (CI) using a random-effects model.
RESULTS
A total of 14 studies were included. The overall incidence of DILI was 4.94 per 100 000 person-years (95% CI 4.05-5.83). Time-based cumulative meta-analysis suggested that the incidence of DILI increased over time since 2010. The incidence varied by regions, with Asia having the highest incidence of 17.82 per 100 000 person-years (95% CI 6.26-29.38), while North America having the lowest incidence of 1.72 per 100 000 person-years (95% CI 0.48-2.95). All studies reported a higher incidence of DILI in the elderly but comparable incidences between male and female (3.42 per 100 000 person-years vs 4.64 per 100 000 person-years).
CONCLUSIONS
The global incidence of DILI has been increasing since 2010, with the highest incidence in Asia. Understanding the epidemiological characteristics of DILI helps establish specific strategies to deal with this emerging health problems.
Topics: Humans; Male; Female; Aged; Incidence; Chemical and Drug Induced Liver Injury
PubMed: 37460777
DOI: 10.1111/1751-2980.13205 -
Critical Care (London, England) Jun 2021β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension....
BACKGROUND
β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning.
METHODS
We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods.
RESULTS
A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations.
CONCLUSIONS
BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.
Topics: Adrenergic beta-Antagonists; Consensus; Drug Overdose; Extracorporeal Membrane Oxygenation; Humans
PubMed: 34112223
DOI: 10.1186/s13054-021-03585-7 -
Environmental Science and Pollution... May 2022The relationship between toxic metals in the environment and clinical stroke risk remains unclear, although their role as immunotoxicants and carcinogens has been well... (Meta-Analysis)
Meta-Analysis Review
The relationship between toxic metals in the environment and clinical stroke risk remains unclear, although their role as immunotoxicants and carcinogens has been well established. We conducted a systematic review of the relationship between five metals (arsenic, mercury, copper, cadmium, and lead) and stroke. First, we comprehensively searched 3 databases (Pubmed, EMBASE, and Cochrane) from inception until June 2021. Random-effects meta-analyses, pooled relative risks (RR) and 95% confidence intervals (CI) were applied to evaluate the effect value. We finally identified 38 studies involving 642,014 non-overlapping participants. Comparing the highest vs. lowest baseline levels, chronic exposure to lead (RR = 1.07; 95%CI,1.00-1.14), cadmium (RR = 1.30; 95%CI,1.13-1.48), and copper (RR = 1.19; 95%CI,1.04-1.36) were significantly associated with stroke risks. However, the other two metals (arsenic and mercury) had less effect on stroke risk. Further analysis indicated that the association was likely in a metal dose-dependent manner. The results may further support the possibility that environmental toxic metal contaminants in recent years are associated with the increased risk of stroke.
Topics: Arsenic; Cadmium; Copper; Heavy Metal Poisoning; Humans; Lead; Mercury; Stroke
PubMed: 35190994
DOI: 10.1007/s11356-022-18866-z -
The Lancet. Infectious Diseases Nov 2014Listeriosis, caused by Listeria monocytogenes, is an important foodborne disease that can be difficult to control and commonly results in severe clinical outcomes. We... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Listeriosis, caused by Listeria monocytogenes, is an important foodborne disease that can be difficult to control and commonly results in severe clinical outcomes. We aimed to provide the first estimates of global numbers of illnesses, deaths, and disability-adjusted life-years (DALYs) due to listeriosis, by synthesising information and knowledge through a systematic review.
METHODS
We retrieved data on listeriosis through a systematic review of peer-reviewed and grey literature (published in 1990-2012). We excluded incidence data from before 1990 from the analysis. We reviewed national surveillance data where available. We did a multilevel meta-analysis to impute missing country-specific listeriosis incidence rates. We used a meta-regression to calculate the proportions of health states, and a Monte Carlo simulation to generate DALYs by WHO subregion.
FINDINGS
We screened 11,722 references and identified 87 eligible studies containing listeriosis data for inclusion in the meta-analyses. We estimated that, in 2010, listeriosis resulted in 23,150 illnesses (95% credible interval 6061-91,247), 5463 deaths (1401-21,497), and 172,823 DALYs (44,079-676,465). The proportion of perinatal cases was 20·7% (SD 1·7).
INTERPRETATION
Our quantification of the global burden of listeriosis will enable international prioritisation exercises. The number of DALYs due to listeriosis was lower than those due to congenital toxoplasmosis but accords with those due to echinococcosis. Urgent efforts are needed to fill the missing data in developing countries. We were unable to identify incidence data for the AFRO, EMRO, and SEARO WHO regions.
FUNDING
WHO Foodborne Diseases Epidemiology Reference Group and the Université catholique de Louvain.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Foodborne Diseases; Global Health; Humans; Incidence; Infant; Listeria monocytogenes; Listeriosis; Male; Middle Aged; Young Adult
PubMed: 25241232
DOI: 10.1016/S1473-3099(14)70870-9 -
The Cochrane Database of Systematic... Jun 2018Fluphenazine is one of the first drugs to be classed as an 'antipsychotic' and has been widely available for five decades. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fluphenazine is one of the first drugs to be classed as an 'antipsychotic' and has been widely available for five decades.
OBJECTIVES
To compare the effects of oral fluphenazine with placebo for the treatment of schizophrenia. To evaluate any available economic studies and value outcome data.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (23 July 2013, 23 December 2014, 9 November 2016 and 28 December 2017 ) which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There is no language, date, document type, or publication status limitations for inclusion of records in the register.
SELECTION CRITERIA
We sought all randomised controlled trials comparing oral fluphenazine with placebo relevant to people with schizophrenia. Primary outcomes of interest were global state and adverse effects.
DATA COLLECTION AND ANALYSIS
For the effects of interventions, a review team inspected citations and abstracts independently, ordered papers and re-inspected and quality assessed trials. We extracted data independently. Dichotomous data were analysed using fixed-effect risk ratio (RR) and the 95% confidence interval (CI). Continuous data were excluded if more than 50% of people were lost to follow-up, but, where possible, mean differences (MD) were calculated. Economic studies were searched and reliably selected by an economic review team to provide an economic summary of available data. Where no relevant economic studies were eligible for inclusion, the economic review team valued the already-included effectiveness outcome data to provide a rudimentary economic summary.
MAIN RESULTS
From over 1200 electronic records of 415 studies identified by our initial search and this updated search, we excluded 48 potentially relevant studies and included seven trials published between 1964 and 1999 that randomised 439 (mostly adult participants). No new included trials were identified for this review update. Compared with placebo, global state outcomes of 'not improved or worsened' were not significantly different in the medium term in one small study (n = 50, 1 RCT, RR 1.12 CI 0.79 to 1.58, very low quality of evidence). The risk of relapse in the long term was greater in two small studies in people receiving placebo (n = 86, 2 RCTs, RR 0.39 CI 0.05 to 3.31, very low quality of evidence), however with high degree of heterogeneity in the results. Only one person allocated fluphenazine was reported in the same small study to have died on long-term follow-up (n = 50, 1 RCT, RR 2.38 CI 0.10 to 55.72, low quality of evidence). Short-term extrapyramidal adverse effects were significantly more frequent with fluphenazine compared to placebo in two other studies for the outcomes of akathisia (n = 227, 2 RCTs, RR 3.43 CI 1.23 to 9.56, moderate quality of evidence) and rigidity (n = 227, 2 RCTs, RR 3.54 CI 1.76 to 7.14, moderate quality of evidence). For economic outcomes, we valued outcomes for relapse and presented them in additional tables.
AUTHORS' CONCLUSIONS
The findings in this review confirm much that clinicians and recipients of care already know, but they provide quantification to support clinical impression. Fluphenazine's global position as an effective treatment for psychoses is not threatened by the outcome of this review. However, fluphenazine is an imperfect treatment and if accessible, other inexpensive drugs less associated with adverse effects may be an equally effective choice for people with schizophrenia.
Topics: Administration, Oral; Akathisia, Drug-Induced; Antipsychotic Agents; Fluphenazine; Humans; Placebos; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia
PubMed: 29893410
DOI: 10.1002/14651858.CD006352.pub3 -
European Review For Medical and... Nov 2021To describe a young patient who had a Bothrops envenomation (BE) and evolved with shock and subcapsular liver hematoma. Moreover, a review on BE and liver hematoma was...
OBJECTIVE
To describe a young patient who had a Bothrops envenomation (BE) and evolved with shock and subcapsular liver hematoma. Moreover, a review on BE and liver hematoma was also performed.
PATIENTS AND METHODS
A systematic screening of articles was conducted and all articles on the association between BE and liver hematoma were included. A new case report is added to the published list. The following terms were used: "Bothrops" and "liver hematoma" or "liver hemorrhage."
RESULTS
This literature search found only one article describing one patient with BE and liver hematoma. We performed our analysis by adding our present case, with a total of 2 cases. Both patients came from Brazil. One of them needed blood transfusions. They both had a good outcome.
CONCLUSIONS
We systematically reviewed all published cases of BE and liver hematoma. It is a rare manifestation of ophidism. Physicians should be alert for patients with shock or abdominal pain after BE; they need to perform an ultrasound to exclude liver hematoma.
Topics: Aged; Animals; Bothrops; Female; Hematoma; Humans; Liver Diseases; Male; Middle Aged; Snake Bites
PubMed: 34859853
DOI: 10.26355/eurrev_202111_27240 -
Nutrients May 2018Caffeine is the most widely consumed psychoactive compound worldwide. It is mostly found in coffee, tea, energizing drinks and in some drugs. However, it has become... (Review)
Review
Caffeine is the most widely consumed psychoactive compound worldwide. It is mostly found in coffee, tea, energizing drinks and in some drugs. However, it has become really easy to obtain pure caffeine (powder or tablets) on the Internet markets. Mechanisms of action are dose-dependent. Serious toxicities such as seizure and cardiac arrhythmias, seen with caffeine plasma concentrations of 15 mg/L or higher, have caused poisoning or, rarely, death; otherwise concentrations of 3⁻6 mg/kg are considered safe. Caffeine concentrations of 80⁻100 mg/L are considered lethal. The aim of this systematic review, performed following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement for the identification and selection of studies, is to review fatal cases in which caffeine has been recognized as the only cause of death in order to identify potential categories at risk. A total of 92 cases have been identified. These events happened more frequently in infants, psychiatric patients, and athletes. Although caffeine intoxication is relatively uncommon, raising awareness about its lethal consequences could be useful for both clinicians and pathologists to identify possible unrecognized cases and prevent related severe health conditions and deaths.
Topics: Caffeine; Coffee; Humans; Poisoning; Tea
PubMed: 29757951
DOI: 10.3390/nu10050611 -
Medicine Dec 2023Menopause causes a variety of symptoms such as hot flashes and night sweats. While menopausal hormonal therapy has been used for managing postmenopausal vasomotor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Menopause causes a variety of symptoms such as hot flashes and night sweats. While menopausal hormonal therapy has been used for managing postmenopausal vasomotor symptoms (VMS) for quite a while, it has a considerably poor safety profile.
OBJECTIVE
To review and analyze existing data to evaluate the efficacy of the neurokinin-3 antagonist, fezolinetant, in treating postmenopausal VMS and to assess its safety profile.
METHODS
A thorough literature search was performed on PubMed, Cochrane Library, and Google Scholar in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020, to find publications on the efficacy of fezolinetant for postmenopausal VMS. Changes in the frequency and severity scores of moderate/severe VMS and changes in the Hot Flash-Related Daily Interference Scale (HFRDIS), Greene Climacteric Scale (GCS), and Menopause-Specific Quality of Life (MENQoL) were the efficacy outcomes. Adverse events, drug-related treatment-emergent adverse effects (TEAEs), drug-related dropouts, hepatotoxicity, endometrial hyperplasia or tumor, and uterine bleeding were all safety outcomes. We used Review Manager 5.4 for pooling risk ratios (RRs) and mean differences (MDs) for dichotomous and continuous outcomes, respectively. A P value of < .05 was considered significant.
RESULTS
There was a significant reduction in mean daily VMS frequency at weeks 4 and 12 (MD, -2.36; 95% confidence interval [CI], -2.85 to -1.87; P < .00001, for week 12) and also a significant decrease in VMS severity scores in the treatment group. Furthermore, improvements in MENQoL, HFRDIS, and GCS scores were observed. There was no significant difference in adverse events while drug-related TEAEs (RR, 1.21; 95% CI, 0.90-1.63; P = .21) showed a slight increase with fezolinetant. Drug-related dropouts were again similar across the 2 groups. Uterine bleeding had a lower incidence while endometrial events and hepatotoxicity showed a statistically insignificant, increasing trend in the fezolinetant group.
DISCUSSION AND IMPLICATIONS
Fezolinetant can be a treatment option for postmenopausal VMS but warns of a risk increase in endometrial hyperplasia or tumors. The heterogeneity in the data being analyzed, short follow-up period, and small sample size in most of the included randomized controlled trials were the greatest limitations, which must be considered in further research and safety profile exploration.
Topics: Female; Humans; Postmenopause; Endometrial Hyperplasia; Quality of Life; Menopause; Hot Flashes; Uterine Hemorrhage; Chemical and Drug Induced Liver Injury
PubMed: 38115258
DOI: 10.1097/MD.0000000000036592