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Evidence-based Complementary and... 2019Chemotherapy-induced peripheral neuropathy (CIPN) remains as a big unsolved challenge for cancer patients and oncologists. However, there is no effective treatment to... (Review)
Review
BACKGROUND
Chemotherapy-induced peripheral neuropathy (CIPN) remains as a big unsolved challenge for cancer patients and oncologists. However, there is no effective treatment to prevent and cure it. This systematic review and meta-analysis chiefly aimed to assess the effectiveness and safety on the method of activating blood and dredging collaterals in traditional Chinese medicine (TCM) for reducing CIPN.
METHODS
Two authors comprehensively searched all the randomized controlled trials (RCTs) via PubMed, Cochrane, China National Knowledge Infrastructure (CNKI), and Wanfang Database of China Science Periodical Database (CSPD). The Review Manager (RevMan) 5.0 was used to conduct the meta-analysis.
RESULTS
20 trials including 1481 participants were analyzed. 15 trials tested the incidence of all-grade CIPN which was significantly lower in intervention arm and 16 trails presented that the result of high-grade CIPN was the same. The total effective rate of the use of Chinese herbs was 77.19% versus 45.79% in the comparator group. Besides, the use of Chinese herbs statistically promoted the sensory nerve conduction velocity (SNCV) and the motor nerve conduction velocity (MNCV). Besides, the quality of life (QoL) in the intervention group was better than the comparator one. Herbs-related adverse events were skin allergy, skin chap, and scald, which could be managed well.
CONCLUSIONS
The work involving studies of the effectiveness and safety on TCM for reducing CIPN proves to be encouraging. Herbs with the function of activating blood and dredging collaterals were found to potentially promote the curative effects as well as making improvements of SNCV and MNCV. However, in the future, more double-blind, multicenter, large-scale RCTs and more comprehensive researches are still required.
PubMed: 31281395
DOI: 10.1155/2019/1029626 -
The Cochrane Database of Systematic... Aug 2022This is an updated version of the Cochrane Review first published in 2011, and most recently updated in 2019. Epilepsy is a chronic and disabling neurological disorder,... (Review)
Review
BACKGROUND
This is an updated version of the Cochrane Review first published in 2011, and most recently updated in 2019. Epilepsy is a chronic and disabling neurological disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available antiepileptic drugs and require treatment with multiple antiepileptic drugs in combination. Felbamate is a second-generation antiepileptic drug that can be used as add-on therapy to standard antiepileptic drugs.
OBJECTIVES
To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with drug-resistant focal-onset epilepsy.
SEARCH METHODS
For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 13 July 2021) on 15 July 2021. There were no language or time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies.
SELECTION CRITERIA
We searched for randomised placebo-controlled add-on studies of people of any age with drug-resistant focal seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel-group or cross-over design.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion and extracted information. In the case of disagreements, a third review author arbitrated. Review authors assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life.
MAIN RESULTS
We included four randomised controlled trials, representing a total of 236 participants, in the review. Two trials had parallel-group design, the third had a two-period cross-over design, and the fourth had a three-period cross-over design. We judged all four studies to be at an unclear risk of bias overall. Bias arose from the incomplete reporting of methodological details, the incomplete and selective reporting of outcome data, and from participants having unstable drug regimens during experimental treatment in one trial. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the extracted data. Only one study reported the outcome of 50% or greater reduction in seizure frequency, whilst three studies reported percentage reduction in seizure frequency compared to placebo. One study claimed an average seizure reduction of 35.8% with add-on felbamate whilst another study claimed a more modest reduction of 4.2%. Both studies reported that seizure frequency increased with add-on placebo and that there was a significant difference in seizure reduction between felbamate and placebo (P = 0.0005 and P = 0.018, respectively). The third study reported a 14% reduction in seizure frequency with add-on felbamate but stated that the difference between treatments was not significant. There were conflicting results regarding treatment withdrawal. One study reported a higher treatment withdrawal for placebo-randomised participants, whereas the other three studies reported higher treatment withdrawal rates for felbamate-randomised participants. Notably, the treatment withdrawal rates for felbamate treatment groups across all four studies remained reasonably low (less than 10%), suggesting that felbamate may be well tolerated. Felbamate-randomised participants most commonly withdrew from treatment due to adverse effects. The adverse effects consistently reported by all four studies were headache, dizziness and nausea. All three adverse effects were reported by 23% to 40% of felbamate-treated participants versus 3% to 15% of placebo-treated participants. We assessed the evidence for all outcomes using GRADE and rated the evidence as very low certainty, meaning that we have little confidence in the findings reported. We mainly downgraded evidence for imprecision due to the narrative synthesis conducted and the low number of events. We stress that the true effect of felbamate could likely be significantly different from that reported in this current review update.
AUTHORS' CONCLUSIONS
In view of the methodological deficiencies, the limited number of included studies and the differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add-on therapy in people with drug-resistant focal-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.
Topics: Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Epilepsies, Partial; Felbamate; Humans; Quality of Life; Randomized Controlled Trials as Topic; Seizures; Single-Blind Method
PubMed: 35914010
DOI: 10.1002/14651858.CD008295.pub6 -
The Cochrane Database of Systematic... Oct 2016Opioid drugs, including fentanyl, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids... (Review)
Review
BACKGROUND
Opioid drugs, including fentanyl, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids together. This review sought evidence specifically for fentanyl, at any dose, and by any route of administration. Other opioids are considered in separate reviews.
OBJECTIVES
To assess the analgesic efficacy of fentanyl for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to June 2016, together with the reference lists of retrieved articles, and two online study registries.
SELECTION CRITERIA
We included randomised, double-blind studies of two weeks' duration or longer, comparing fentanyl (in any dose, administered by any route, and in any formulation) with placebo or another active treatment in chronic neuropathic pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE.
MAIN RESULTS
Only one study met our inclusion criteria. Participants were men and women (mean age 67 years), with postherpetic neuralgia, complex regional pain syndrome, or chronic postoperative pain. They were experiencing inadequate relief from non-opioid analgesics, and had not previously taken opioids for their neuropathic pain. The study used an enriched enrolment randomised withdrawal design. It was adequately blinded, but we judged it at unclear risk of bias for other criteria.Transdermal fentanyl (one-day fentanyl patch) was titrated over 10 to 29 days to establish the maximum tolerated and effective dose (12.5 to 50 µg/h). Participants who achieved a prespecified good level of pain relief with a stable dose of fentanyl, without excessive use of rescue medication or intolerable adverse events ('responders'), were randomised to continue with fentanyl or switch to placebo for 12 weeks, under double-blind conditions. Our prespecified primary outcomes were not appropriate for this study design, but the measures reported do give an indication of the efficacy of fentanyl in this condition.In the titration phase, 1 in 3 participants withdrew because of adverse events or inadequate pain relief, and almost 90% experienced adverse events. Of 258 participants who underwent open-label titration, 163 were 'responders' and entered the randomised withdrawal phase. The number of participants completing the study (and therefore continuing on treatment) without an increase of pain by more than 15/100 was 47/84 (56%) with fentanyl and 28/79 (35%) with placebo. Because only 63% responded sufficiently to enter the randomised withdrawal phase, this implies that only a maximum of 35% of participants entering the study would have had useful pain relief and tolerability with transdermal fentanyl, compared with 22% with placebo. Almost 60% of participants taking fentanyl were 'satisfied' and 'very satisfied' with their treatment at the end of the study, compared with about 40% with placebo. This outcome approximates to our primary outcome of moderate benefit using the Patient Global Impression of Change scale, but the group was enriched for responders and the method of analysis was not clear. The most common adverse events were constipation, nausea, somnolence, and dizziness.There was no information about other types of neuropathic pain, other routes of administration, or comparisons with other treatments.We downgraded the quality of the evidence to very low because there was only one study, with few participants and events, and there was no information about how data from people who withdrew were analysed.
AUTHORS' CONCLUSIONS
There is insufficient evidence to support or refute the suggestion that fentanyl works in any neuropathic pain condition.
Topics: Aged; Analgesics, Opioid; Female; Fentanyl; Humans; Male; Neuralgia; Pain Measurement; Randomized Controlled Trials as Topic
PubMed: 27727431
DOI: 10.1002/14651858.CD011605.pub2 -
Integrative Cancer Therapies 2022Remote medical scent detection of cancer and infectious diseases with dogs and rats has been an increasing field of research these last 20 years. If validated, the... (Review)
Review
BACKGROUND
Remote medical scent detection of cancer and infectious diseases with dogs and rats has been an increasing field of research these last 20 years. If validated, the possibility of implementing such a technique in the clinic raises many hopes. This systematic review was performed to determine the evidence and performance of such methods and assess their potential relevance in the clinic.
METHODS
Pubmed and Web of Science databases were independently searched based on PRISMA standards between 01/01/2000 and 01/05/2021. We included studies aiming at detecting cancers and infectious diseases affecting humans with dogs or rats. We excluded studies using other animals, studies aiming to detect agricultural diseases, diseases affecting animals, and others such as diabetes and neurodegenerative diseases. Only original articles were included. Data about patients' selection, samples, animal characteristics, animal training, testing configurations, and performances were recorded.
RESULTS
A total of 62 studies were included. Sensitivity and specificity varied a lot among studies: While some publications report low sensitivities of 0.17 and specificities around 0.29, others achieve rates of 1 sensitivity and specificity. Only 6 studies were evaluated in a double-blind screening-like situation. In general, the risk of performance bias was high in most evaluated studies, and the quality of the evidence found was low.
CONCLUSIONS
Medical detection using animals' sense of smell lacks evidence and performances so far to be applied in the clinic. What odors the animals detect is not well understood. Further research should be conducted, focusing on patient selection, samples (choice of materials, standardization), and testing conditions. Interpolations of such results to free running detection (direct contact with humans) should be taken with extreme caution. Considering this synthesis, we discuss the challenges and highlight the excellent odor detection threshold exhibited by animals which represents a potential opportunity to develop an accessible and non-invasive method for disease detection.
Topics: Humans; Dogs; Animals; Rats; Odorants; Neoplasms; Smell; Communicable Diseases; Randomized Controlled Trials as Topic
PubMed: 36541180
DOI: 10.1177/15347354221140516 -
Trials Mar 2017There is no consensus on the preferred method for defining the non-inferiority margin in non-inferiority trials, and previous studies showed that the rationale for its... (Review)
Review
BACKGROUND
There is no consensus on the preferred method for defining the non-inferiority margin in non-inferiority trials, and previous studies showed that the rationale for its choice is often not reported. This study investigated how the non-inferiority margin is defined in the published literature, and whether its reporting has changed over time.
METHODS
A systematic PubMed search was conducted for all published randomized, double-blind, non-inferiority trials from January 1, 1966, to February 6, 2015. The primary outcome was the number of margins that were defined by methods other than the historical evidence of the active comparator. This was evaluated for a time trend. We also assessed the under-reporting of the methods of defining the margin as a secondary outcome, and whether this changed over time. Both outcomes were analyzed using a Poisson log-linear model. Predictors for better reporting of the methods, and the use of the fixed-margin method (one of the historical evidence methods) were also analyzed using logistic regression.
RESULTS
Two hundred seventy-three articles were included, which account for 273 non-inferiority margins. There was no statistically significant difference in the number of margins that were defined by other methods compared to those defined based on the historical evidence (ratio 2.17, 95% CI 0.86 to 5.82, p = 0.11), and this did not change over time. The number of margins for which methods were unreported was similar to those with reported methods (ratio 1.35, 95% CI 0.76 to 2.43, p = 0.31), with no change over time. The method of defining the margin was less often reported in journals with low-impact factors compared to journals with high-impact factors (OR 0.20; 95% CI 0.10 to 0.37, p < 0.0001). The publication of the FDA draft guidance in 2010 was associated with increased reporting of the fixed-margin method (after versus before 2010) (OR 3.54; 95% CI 1.12 to 13.35, p = 0.04).
CONCLUSIONS
Non-inferiority margins are not commonly defined based on the historical evidence of the active comparator, and they are poorly reported. Authors, reviewers, and editors need to take notice of reporting this critical information to allow for better judgment of non-inferiority trials.
Topics: Data Interpretation, Statistical; Double-Blind Method; Equivalence Trials as Topic; Humans; Models, Statistical; Randomized Controlled Trials as Topic; Research Design
PubMed: 28270184
DOI: 10.1186/s13063-017-1859-x -
Medicine Sep 2016The aim of this systematic review was to update, complete, and critically evaluate the evidence from placebo-controlled randomized clinical trials (RCTs) of ginseng for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The aim of this systematic review was to update, complete, and critically evaluate the evidence from placebo-controlled randomized clinical trials (RCTs) of ginseng for managing menopausal women's health.
METHODS
We searched the literature using 13 databases (MEDLINE, AMED, EMBASE, the Cochrane Library, 6 Korean Medical, and 3 Chinese Databases) from their inception to July 2016 and included all double-blind RCTs that compared any type of ginseng with a placebo control in postmenopausal women. The methodological quality of all studies was assessed using a Cochrane risk of bias tool.
RESULTS
Ten RCTs met our inclusion criteria. Most RCTs had unclear risk of bias. One RCT did not show a significant difference in hot flash frequency between Korean red ginseng (KRG) and placebo. The second RCT reported positive effects of KRG on menopausal symptoms. The third RCT found beneficial effects of ginseng (Ginsena) on depression, well-being, and general health. Four RCTs failed to show significant differences in various hormones between KRG and placebo controls except dehydroepiandrosterone. Two other RCTs failed to show effects of KRG on endometrial thickness in menopausal women. The other RCT also failed to show the effects of American ginseng on oxidative stress markers and other antioxidant enzymes.
CONCLUSION
Our systematic review provided positive evidence of ginseng for sexual function and KRG for sexual arousal and total hot flashes score in menopausal women. However, the results of KRG or ginseng failed to show specific effects on hot flash frequency, hormones, biomarkers, or endometrial thickness. The level of evidence for these findings was low because of unclear risk of bias.
Topics: Complementary Therapies; Double-Blind Method; Female; Humans; Menopause; Panax; Phytotherapy; Plant Extracts; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; Women's Health
PubMed: 27661038
DOI: 10.1097/MD.0000000000004914 -
The Cochrane Database of Systematic... May 2018Cerebral palsy occurs in up to 2.1 of every 1000 live births and encompasses a range of motor problems and movement disorders. One commonly occurring movement disorder... (Review)
Review
BACKGROUND
Cerebral palsy occurs in up to 2.1 of every 1000 live births and encompasses a range of motor problems and movement disorders. One commonly occurring movement disorder amongst those with cerebral palsy is dystonia: sustained or intermittent involuntary muscle spasms and contractions that cause twisting, repetitive movements and abnormal postures. The involuntary contractions are often very painful and distressing and cause significant limitations to activity and participation.Oral medications are often the first line of medical treatment for dystonia. Trihexyphenidyl is one such medication that clinicians often use to treat dystonia in people with cerebral palsy.
OBJECTIVES
To assess the effects of trihexyphenidyl in people with dystonic cerebral palsy, according to the World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF) domains of impairment, activity and participation. We also assessed the type and incidence of adverse effects in people taking the drug.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, eight other databases and two trials registers in May 2017, and we checked reference lists and citations to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials comparing oral trihexyphenidyl versus placebo for dystonia in cerebral palsy. We included studies in children and adults of any age with dystonic cerebral palsy, either in isolation or with the associated movement disorders of spasticity, ataxia, chorea, athetosis and/or hypotonia. We included studies regardless of whether or not the study authors specified the method used to diagnose dystonia in their study population. Primary outcomes were change in dystonia and adverse effects. Secondary outcomes were: activity, including mobility and upper limb function; participation in activities of daily living; pain; and quality of life.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified one study, which was set in Australia, that met the inclusion criteria. This was a randomised, double-blind, placebo-controlled, cross-over trial in 16 children (10 boys and 6 girls) with predominant dystonic cerebral palsy and a mean age of 9 years (standard deviation 4.3 years, range 2 to 17 years). We considered the trial to be at low risk of selection, performance, detection, attrition, reporting and other sources of bias. We rated the GRADE quality of the evidence as low.We found no difference in mean follow-up scores for change in dystonia as measured by the Barry Albright Dystonia Scale (BADS), which assesses eight body regions for dystonia on a 5-point scale (0 = none to 4 = severe), resulting in a total score of 0 to 32. The BADS score was 2.67 points higher (95% confidence interval (CI) -2.55 to 7.90; low-quality evidence), that is, worse dystonia, in the treated group. Trihexyphenidyl may be associated with an increased risk of adverse effects (risk ratio 2.54, 95% CI 1.38 to 4.67; low-quality evidence).There was no difference in mean follow-up scores for upper limb function as measured by the Quality of Upper Extremity Skills Test, which has four domains that collectively assess 36 items (each scored 1 or 2) and produces a total score of 0 to 100. The score in the treated group was 4.62 points lower (95% CI -10.98 to 20.22; low-quality evidence), corresponding to worse function, than in the control group. We found low-quality evidence for improved participation (as represented by higher scores) in the treated group in activities of daily living, as measured by three tools: 18.86 points higher (95% CI 5.68 to 32.03) for the Goal Attainment Scale (up to five functional goals scored on 5-point scale (-2 = much less than expected to +2 = much more than expected)), 2.91 points higher (95% CI 1.01 to 4.82) for the satisfaction subscale of the Canadian Occupational Performance Measure (COPM; satisfaction with performance in up to five problem areas scored on a 10-point scale (1 = not satisfied at all to 10 = extremely satisfied)), and 2.24 points higher (95% CI 0.64 to 3.84) for performance subscale of the COPM (performance in up to five problem areas scored on a 10-point scale (1 = not able to do to; 10 = able to do extremely well)).The study did not report on pain or quality of life.
AUTHORS' CONCLUSIONS
At present, there is insufficient evidence regarding the effectiveness of trihexyphenidyl for people with cerebral palsy for the outcomes of: change in dystonia, adverse effects, increased upper limb function and improved participation in activities of daily living. The study did not measure pain or quality of life. There is a need for larger randomised, controlled, multicentre trials that also examine the effect on pain and quality of life in order to determine the effectiveness of trihexyphenidyl for people with cerebral palsy.
Topics: Adolescent; Anti-Dyskinesia Agents; Cerebral Palsy; Child; Child, Preschool; Dystonia; Female; Humans; Male; Trihexyphenidyl
PubMed: 29763510
DOI: 10.1002/14651858.CD012430.pub2 -
The Cochrane Database of Systematic... May 2017Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Neuropathic pain often includes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Neuropathic pain often includes symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the nervous system. Opioid drugs, including morphine, are commonly used to treat neuropathic pain. Most reviews have examined all opioids together. This review sought evidence specifically for morphine; other opioids are considered in separate reviews.
OBJECTIVES
To assess the analgesic efficacy and adverse events of morphine for chronic neuropathic pain in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase for randomised controlled trials from inception to February 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries.
SELECTION CRITERIA
We included randomised, double-blind trials of two weeks' duration or longer, comparing morphine (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH). We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables.
MAIN RESULTS
We identified five randomised, double-blind, cross-over studies with treatment periods of four to seven weeks, involving 236 participants in suitably characterised neuropathic pain; 152 (64%) participants completed all treatment periods. Oral morphine was titrated to maximum daily doses of 90 mg to 180 mg or the maximum tolerated dose, and then maintained for the remainder of the study. Participants had experienced moderate or severe neuropathic pain for at least three months. Included studies involved people with painful diabetic neuropathy, chemotherapy-induced peripheral neuropathy, postherpetic neuralgia criteria, phantom limb or postamputation pain, and lumbar radiculopathy. Exclusions were typically people with other significant comorbidity or pain from other causes.Overall, we judged the studies to be at low risk of bias, but there were concerns over small study size and the imputation method used for participants who withdrew from the studies, both of which could lead to overestimation of treatment benefits and underestimation of harm.There was insufficient or no evidence for the primary outcomes of interest for efficacy or harm. Four studies reported an approximation of moderate pain improvement (any pain-related outcome indicating some improvement) comparing morphine with placebo in different types of neuropathic pain. We pooled these data in an exploratory analysis. Moderate improvement was experienced by 63% (87/138) of participants with morphine and 36% (45/125) with placebo; the risk difference (RD) was 0.27 (95% confidence interval (CI) 0.16 to 0.38, fixed-effects analysis) and the NNT 3.7 (2.6 to 6.5). We assessed the quality of the evidence as very low because of the small number of events; available information did not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different was very high. A similar exploratory analysis for substantial pain relief on three studies (177 participants) showed no difference between morphine and placebo.All-cause withdrawals in four studies occurred in 16% (24/152) of participants with morphine and 12% (16/137) with placebo. The RD was 0.04 (-0.04 to 0.12, random-effects analysis). Adverse events were inconsistently reported, more common with morphine than with placebo, and typical of opioids. There were two serious adverse events, one with morphine, and one with a combination of morphine and nortriptyline. No deaths were reported. These outcomes were assessed as very low quality because of the limited number of participants and events.
AUTHORS' CONCLUSIONS
There was insufficient evidence to support or refute the suggestion that morphine has any efficacy in any neuropathic pain condition.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Chronic Pain; Humans; Middle Aged; Morphine; Neuralgia; Numbers Needed To Treat; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28530786
DOI: 10.1002/14651858.CD011669.pub2 -
Pharmacological Research Feb 2021Conducting randomised clinical trials (RCTs) in idiosyncratic drug-induced liver injury (DILI) is challenging. This systematic review aims to summarise the design and... (Meta-Analysis)
Meta-Analysis
Conducting randomised clinical trials (RCTs) in idiosyncratic drug-induced liver injury (DILI) is challenging. This systematic review aims to summarise the design and findings of RCTs in the prevention and management of idiosyncratic DILI. A systematic literature search up to January 31, 2020 was performed. Recognised scales were used to assess methodological bias and quality of the studies. Quantitative and qualitative analyses were performed. Heterogeneity was assessed with I statistic. Overall, 22 RCTs were included: 12 on prevention (n = 2,471 patients) and 10 in management (n = 797) of DILI/non-acetaminophen DILI-related acute liver failure (ALF). Silymarin (eight studies), bicyclol (four), magnesium isoglycyrrhizinate (three), N-acetylcysteine (three), tiopronin (one), L-carnitine (one), and traditional Chinese medicines (two) were tested in the intervention arm, while control arm mostly received standard supportive care or placebo. Main efficacy criteria in the prevention RCTs was DILI incidence or peak of liver enzymes value. In management RCTs, the efficacy parameter was usually 50 % decrease or normalisation of liver enzymes, or survival rate in DILI-related ALF patients. Overall, 15 trials described the randomisation method, eight were double-blind (n = 672) and nine had sample size estimation (n = 880). Four RCTs involving 377 patients used an intention-to-treat analysis. Based on the scarce number of trials available, tested agents showed limited efficacy in DILI prevention and management and a favourable safety profile. In conclusion, heterogeneity among studies in DILI case qualification and methodologic quality was evident, and the RCTs performed demonstrated limited efficacy of specific interventions. International research networks are needed to establish a framework on RCTs design and therapeutic endpoints.
Topics: Chemical and Drug Induced Liver Injury; Humans; Protective Agents; Randomized Controlled Trials as Topic
PubMed: 33359912
DOI: 10.1016/j.phrs.2020.105404 -
Nature and Science of Sleep 2021Obstructive sleep apnea (OSA) is a highly prevalent disease with substantial public health burden. In most of the cases, there is a genetic predisposition to OSA.... (Review)
Review
Polymorphism of the Serotonin Transporter Gene and the Peripheral 5-Hydroxytryptamine in Obstructive Sleep Apnea: What Do We Know and What are We Looking for? A Systematic Review of the Literature.
BACKGROUND
Obstructive sleep apnea (OSA) is a highly prevalent disease with substantial public health burden. In most of the cases, there is a genetic predisposition to OSA. Serotonin/T-HydroxyTriptamine (5-HT) plays a key role in ventilatory stimulation, while the polymorphism of the serotonin transporter gene (STG) leads to alterations in serotonin level, making it important in OSA.
OBJECTIVE
To examine whether the 5-HydroxyTriptamine and the genetic predisposition influence the incidence and evolution of OSA, we reviewed randomized, controlled trials and observational studies on the selected topic. The secondary objective was to determine the metabolic effects of the circulating serotonin in other tissues (liver, pancreas, gut, brown adipose tissue, and white adipose tissue) and its role in the development of obesity.
DATA SOURCES
A systematic review of English articles was performed based on PubMed and the Cochrane Library databases. Search filters included randomized controlled trial, controlled clinical trial, random allocation, double-blind method, and case-control studies and used the following keywords: Brain Serotonin OR Serotonin Transporter Gene Polymorphism OR Peripheral 5-HydroxyTryptamine AND Obstructive Sleep Apnea OR Sleep Disorder Breathing OR brain serotonin AND OSA OR serotonin transporter gene OR Peripheral 5-Hydroxytryptamine AND Sleep.
STUDY ELIGIBILITY CRITERIA
The inclusion criteria for the current review were previous diagnosis of OSA, age above 18 years, and articles including quantitative data about serotonin transporter gene or peripheral serotonin. Language and time criteria were added - English articles published in the last 15 years. Studies that were not included were reviews and case reports.
STUDY APPRAISAL AND SYNTHESIS METHODS
In order to study the serotonin function, a literature research was conducted in the databases Pubmed and Cochrane Library. The following search terms were used: serotonin, 5-hydroxytryptamine, serotonin transporter gene. A critical appraisal of the included studies was performed with the Newcastle-Ottawa scale (NOS) and Delphi list.
RESULTS
The search yielded 1210 articles, from which 43 were included. The included studies suggest that the two polymorphisms of serotonin transporter gene (5HTT) - variable number of tandem repeats (VNTR) and linked polymorphic region (LPR) - are strong candidates in the pathogenesis of OSA. The allele 10 of 5HTTVNTR and the long/long (L/L) allele genotype were associated with a higher prevalence of OSA and the L allele with a higher apnea-hypopnea index and a longer time during sleep with oxygen desaturation.
LIMITATIONS
The main limitation of the present study consists of heterogeneity of the information. Being a less studied subject, randomized trials are not widely available and most data were obtained from case-control trials. Moreover, the included material indirectly approached the subject by demonstrating the effects of serotoninergic system over the metabolism, the connection between serotonin and obesity, factors which are implied in the pathogenesis of OSA.
CONCLUSION AND IMPLICATIONS OF KEY FINDINGS
The two polymorphisms of serotonin gene can be considered important factors in the diagnosis and management of OSA.
PubMed: 33603523
DOI: 10.2147/NSS.S278170