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The Cochrane Database of Systematic... Jun 2024Constipation that is prolonged and does not resolve with conventional therapeutic measures is called intractable constipation. The treatment of intractable constipation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Constipation that is prolonged and does not resolve with conventional therapeutic measures is called intractable constipation. The treatment of intractable constipation is challenging, involving pharmacological or non-pharmacological therapies, as well as surgical approaches. Unresolved constipation can negatively impact quality of life, with additional implications for health systems. Consequently, there is an urgent need to identify treatments that are efficacious and safe.
OBJECTIVES
To evaluate the efficacy and safety of treatments used for intractable constipation in children.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and two trials registers up to 23 June 2023. We also searched reference lists of included studies for relevant studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing any pharmacological, non-pharmacological, or surgical treatment to placebo or another active comparator, in participants aged between 0 and 18 years with functional constipation who had not responded to conventional medical therapy.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were symptom resolution, frequency of defecation, treatment success, and adverse events; secondary outcomes were stool consistency, painful defecation, quality of life, faecal incontinence frequency, abdominal pain, hospital admission for disimpaction, and school absence. We used GRADE to assess the certainty of evidence for each primary outcome.
MAIN RESULTS
This review included 10 RCTs with 1278 children who had intractable constipation. We assessed one study as at low risk of bias across all domains. There were serious concerns about risk of bias in six studies. One study compared the injection of 160 units botulinum toxin A (n = 44) to unspecified oral stool softeners (n = 44). We are very uncertain whether botulinum toxin A injection improves treatment success (risk ratio (RR) 37.00, 95% confidence interval (CI) 5.31 to 257.94; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Frequency of defecation was reported only for the botulinum toxin A injection group (mean interval of 2.6 days). The study reported no data for the other primary outcomes. One study compared erythromycin estolate (n = 6) to placebo (n = 8). The only primary outcome reported was adverse events, which were 0 in both groups. The evidence is of very low certainty due to concerns with risk of bias and serious imprecision. One study compared 12 or 24 μg oral lubiprostone (n = 404) twice a day to placebo (n = 202) over 12 weeks. There may be little to no difference in treatment success (RR 1.29, 95% CI 0.87 to 1.92; low certainty evidence). We also found that lubiprostone probably results in little to no difference in adverse events (RR 1.05, 95% CI 0.91 to 1.21; moderate certainty evidence). The study reported no data for the other primary outcomes. One study compared three-weekly rectal sodium dioctyl sulfosuccinate and sorbitol enemas (n = 51) to 0.5 g/kg/day polyethylene glycol laxatives (n = 51) over a 52-week period. We are very uncertain whether rectal sodium dioctyl sulfosuccinate and sorbitol enemas improve treatment success (RR 1.33, 95% CI 0.83 to 2.14; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Results of defecation frequency per week was reported only as modelled means using a linear mixed model. The study reported no data for the other primary outcomes. One study compared biofeedback therapy (n = 12) to no intervention (n = 12). We are very uncertain whether biofeedback therapy improves symptom resolution (RR 2.50, 95% CI 1.08 to 5.79; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). The study reported no data for the other primary outcomes. One study compared 20 minutes of intrarectal electromotive botulinum toxin A using 2800 Hz frequency and botulinum toxin A dose 10 international units/kg (n = 30) to 10 international units/kg botulinum toxin A injection (n = 30). We are very uncertain whether intrarectal electromotive botulinum toxin A improves symptom resolution (RR 0.96, 95% CI 0.76 to 1.22; very low certainty evidence) or if it increases the frequency of defecation (mean difference (MD) 0.00, 95% CI -1.87 to 1.87; very low certainty evidence). We are also very uncertain whether intrarectal electromotive botulinum toxin A has an improved safety profile (RR 0.20, 95% CI 0.01 to 4.00; very low certainty evidence). The evidence for these results is of very low certainty due to serious concerns with risk of bias and imprecision. The study did not report data on treatment success. One study compared the injection of 60 units botulinum toxin A (n = 21) to myectomy of the internal anal sphincter (n = 21). We are very uncertain whether botulinum toxin A injection improves treatment success (RR 1.00, 95% CI 0.75 to 1.34; very low certainty evidence). No adverse events were recorded. The study reported no data for the other primary outcomes. One study compared 0.04 mg/kg oral prucalopride (n = 107) once daily to placebo (n = 108) over eight weeks. Oral prucalopride probably results in little or no difference in defecation frequency (MD 0.50, 95% CI -0.06 to 1.06; moderate certainty evidence); treatment success (RR 0.96, 95% CI 0.53 to 1.72; moderate certainty evidence); and adverse events (RR 1.15, 95% CI 0.94 to 1.39; moderate certainty evidence). The study did not report data on symptom resolution. One study compared transcutaneous electrical stimulation to sham stimulation, and another study compared dietitian-prescribed Mediterranean diet with written instructions versus written instructions. These studies did not report any of our predefined primary outcomes.
AUTHORS' CONCLUSIONS
We identified low to moderate certainty evidence that oral lubiprostone may result in little to no difference in treatment success and adverse events compared to placebo. Based on moderate certainty evidence, there is probably little or no difference between oral prucalopride and placebo in defecation frequency, treatment success, or adverse events. For all other comparisons, the certainty of the evidence for our predefined primary outcomes is very low due to serious concerns with study limitations and imprecision. Consequently, no robust conclusions could be drawn.
Topics: Humans; Constipation; Child; Randomized Controlled Trials as Topic; Child, Preschool; Adolescent; Defecation; Botulinum Toxins, Type A; Quality of Life; Laxatives; Infant; Bias; Lubiprostone
PubMed: 38895907
DOI: 10.1002/14651858.CD014580.pub2 -
Proceedings. Biological Sciences Jun 2024Pesticides have been identified as major drivers of insect biodiversity loss. Thus, the study of their effects on non-pest insect species has attracted a lot of... (Review)
Review
Pesticides have been identified as major drivers of insect biodiversity loss. Thus, the study of their effects on non-pest insect species has attracted a lot of attention in recent decades. In general toxicology, the 'gold standard' to assess the toxicity of a substance is to measure mass-specific LD (i.e. median lethal dose per unit body mass). In entomology, reviews attempting to compare these data across all available studies are lacking. To fill this gap in knowledge, we performed a systematic review of the lethality of imidacloprid for adult insects. Imidacloprid is possibly the most extensively studied insecticide in recent times, yet we found that little is comparable across studies, owing to both methodological divergence and missing estimates of body mass. By accounting for body mass whenever possible, we show how imidacloprid sensitivity spans across an apparent range of approximately six orders of magnitude across insect species. Very high variability within species can also be observed owing to differences in exposure methods and observation time. We suggest that a more comparable and comprehensive approach has both biological and economic relevance. Ultimately, this would help to identify differences that could direct research towards preventing non-target species from being negatively affected.
Topics: Neonicotinoids; Nitro Compounds; Animals; Insecticides; Insecta; Imidazoles; Species Specificity; Lethal Dose 50
PubMed: 38864325
DOI: 10.1098/rspb.2023.2811 -
Frontiers in Public Health 2024Several pharmacological interventions, such as nicotine replacement therapy (NRT), varenicline, and bupropion, have been approved for clinical use of smoking cessation.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Several pharmacological interventions, such as nicotine replacement therapy (NRT), varenicline, and bupropion, have been approved for clinical use of smoking cessation. E-cigarettes (EC) are increasingly explored by many RCTs for their potentiality in smoking cessation. In addition, some RCTs are attempting to explore new drugs for smoking cessation, such as cytisine. This network meta-analysis (NMA) aims to investigate how these drugs and e-cigarettes compare regarding their efficacy and acceptability.
MATERIALS AND METHODS
This systematic review and NMA searched all clinical studies on smoking cessation using pharmacological monotherapies or e-cigarettes published from January 2011 to May 2022 using MEDLINE, COCHRANE Library, and PsychINFO databases. NRTs were divided into transdermal (TDN) and oronasal nicotine (ONN) by administrative routes, thus 7 network nodes were set up for direct and indirect comparison. Two different indicators measured the efficacy: prevalent and continuous smoking abstinence. The drop-out rates measured the acceptability.
RESULTS
The final 40 clinical studies included in this study comprised 77 study cohorts and 25,889 participants. Varenicline is more effective intervention to assist in smoking cessation during 16-32 weeks follow-up, and is very likely to prompt dropout. Cytisine shows more effectiveness in continuous smoking cessation but may also lead to dropout. E-cigarettes and oronasal nicotine are more effective than no treatment in encouraging prevalent abstinence, but least likely to prompt dropout. Finally, transdermal nicotine delivery is more effective than no treatment in continuous abstinence, with neither significant effect on prevalent abstinence nor dropout rate.
CONCLUSION
This review suggested and agreed that Varenicline, Cytisine and transdermal nicotine delivery, as smoking cessation intervention, have advantages and disadvantages. However, we had to have reservations about e-cigarettes as a way to quit smoking in adolescents.
Topics: Humans; Smoking Cessation; Electronic Nicotine Delivery Systems; Varenicline; Network Meta-Analysis; Tobacco Use Cessation Devices; Smoking Cessation Agents; Alkaloids; Azocines; Bupropion; Quinolizines; Nicotine; Quinolizidine Alkaloids
PubMed: 38841681
DOI: 10.3389/fpubh.2024.1361186 -
Archivos Espanoles de Urologia May 2024This systematic review and meta-analysis aimed to compare the effectiveness and safety of submucosal injection of onabotulinum toxin A (OnabotA) with intradetrusor... (Meta-Analysis)
Meta-Analysis Comparative Study
PURPOSE
This systematic review and meta-analysis aimed to compare the effectiveness and safety of submucosal injection of onabotulinum toxin A (OnabotA) with intradetrusor injection for overactive bladder syndrome (OAB).
METHODS
This systematic review is registered with PROSPERO (CRD42021237964). A licensed librarian surveyed Medline, EMBASE, Scopus, and Google Scholar databases to conduct a comprehensive search. Studies comparing suburothelial and intradetrusor techniques of OnabotA injection for OAB were included, along with clinical and urodynamic variables and complications. The studies were assessed for quality on the basis of Cochrane Collaboration guidelines and evaluated using statistical analysis via a random-effect model and I statistic. Data extraction and analysis were conducted using Covidence systematic review platform and Review Manager software.
RESULTS
Six studies with 299 patients were included in the systematic review, with four reporting that suburothelial injection of OnabotA was as effective as intradetrusor injection and two reporting intradetrusor injection to be more effective. The meta-analysis found no significant difference between the suburothelial and intradetrusor groups for mean daily catheter or voiding frequency (mean difference: 2.12 [95% confidence interval (CI): -1.61, 5.84]) and the mean number of urgency/urge incontinence episodes (mean difference: 0.08 [95% CI: -1.42, 1.57]). However, a significant heterogeneity was found among the studies. Only the mean volume at first detrusor contraction showed a significant difference, being higher for suburothelial injection (mean difference: 33.39 [95% CI: 0.16, 66.63]). No significant difference was noted for mean compliance, mean bladder capacity, and mean maximum detrusor pressure. Urinary tract infections (UTIs) ( = 0.24) and acute urinary retention ( = 0.92) showed no significant difference between the two groups. The risk of bias varied among the studies.
CONCLUSIONS
Suburothelial injection of OnabotA is as effective as intradetrusor injection in improving OAB symptoms, and it has similar complication rates. A higher mean volume of the first detrusor contraction was found in a urodynamic study with suburothelial injection.
Topics: Botulinum Toxins, Type A; Humans; Urinary Bladder, Overactive; Adult; Urinary Bladder, Neurogenic; Injections
PubMed: 38840279
DOI: 10.56434/j.arch.esp.urol.20247704.50 -
Pharmaceuticals (Basel, Switzerland) May 2024Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing... (Review)
Review
Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer's disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected twenty-one sources referring to fourteen studies focused on KarXT, out of which only four have available results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data are needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.
PubMed: 38794180
DOI: 10.3390/ph17050610 -
Archives of Dermatological Research May 2024The use of botulinum toxin for off-label indications has become more prevalent, but the specific benefits in Mohs micrographic surgery (MMS) have not yet been fully... (Review)
Review
The use of botulinum toxin for off-label indications has become more prevalent, but the specific benefits in Mohs micrographic surgery (MMS) have not yet been fully elucidated. A systematic review was performed of PubMed, Cochrane, EMBASE, and Scopus databases to identify all articles describing the use of botulinum toxin in MMS. Analysis was subdivided into scar minimization, parotid injury, and pain management. A total of nine articles were included. Scar minimization and treatment of parotid injury were the most reported uses. One case reported the use of botulinum toxin for pain management. Off label uses of botulinum toxin are being explored. Additional research is warranted to determine the efficacy and utility of botulinum toxin in MMS.
Topics: Humans; Mohs Surgery; Off-Label Use; Cicatrix; Skin Neoplasms; Botulinum Toxins, Type A; Botulinum Toxins; Pain Management; Parotid Gland
PubMed: 38787406
DOI: 10.1007/s00403-024-02904-6 -
Toxins May 2024Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson's... (Review)
Review
Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson's disease and atypical Parkinsonism patients. Despite advancements in diagnosing, assessing, and understanding their pathophysiology, managing these complications remains a significant challenge. Often underestimated by healthcare professionals, these disturbances can exacerbate disability. This systematic review assesses botulinum toxin treatments' effectiveness, alone and with rehabilitation, in addressing APAs in Parkinson's disease, utilizing MEDLINE (PubMed), Web of Science, and SCOPUS databases for source material. Of the 1087 records retrieved, 16 met the selection criteria. Most research has focused on botulinum toxin (BoNT) as the primary treatment for camptocormia and Pisa syndrome, utilizing mostly observational methods. Despite dose and injection site variations, a common strategy was using electromyography-guided injections, occasionally enhanced with ultrasound. Patients with Pisa syndrome notably saw consistent improvements in APAs and pain. However, studies on the combined effects of botulinum toxin and rehabilitation are limited, and antecollis is significantly under-researched. These findings recommend precise BoNT injections into hyperactive muscles in well-selected patients by skilled clinicians, avoiding compensatory muscles, and underscore the necessity of early rehabilitation. Rehabilitation is crucial in a multidisciplinary approach to managing APAs, highlighting the importance of a multidisciplinary team of experts.
Topics: Humans; Parkinson Disease; Botulinum Toxins; Neuromuscular Agents; Spinal Curvatures; Posture
PubMed: 38787080
DOI: 10.3390/toxins16050228 -
Toxins May 2024Chronic migraine (CM) significantly affects underage individuals. The study objectives are (1) to analyze the effectiveness and safety of onabotulinumtoxinA (BTX-A) in... (Observational Study)
Observational Study
Chronic migraine (CM) significantly affects underage individuals. The study objectives are (1) to analyze the effectiveness and safety of onabotulinumtoxinA (BTX-A) in adolescents with CM; (2) to review the literature on BTX-A use in the pediatric population. This prospective observational study included patients under 18 years old with CM treated with BTX-A (PREEMPT protocol) as compassionate use. Demographic, efficacy (monthly headache days-MHD; monthly migraine days-MMD; acute medication days/month-AMDM) and side effect data were collected. A ≥ 50% reduction in MHD was considered as a response. Effectiveness and safety were analyzed at 6 and 12 months. A systematic review of the use of BTX-A in children/adolescents was conducted in July 2023. In total, 20 patients were included (median age 15 years [14.75-17], 70% (14/20) females). The median basal frequencies were 28.8 [20-28] MHD, 18 [10-28] MMD and 10 [7.5-21.2] AMDM. Compared with baseline, at 6 months ( = 20), 11 patients (55%) were responders, with a median reduction in MHD of -20 days/month ( = 0.001). At 12 months ( = 14), eight patients (57.1%) were responders, with a median reduction in MHD of -17.5 days/month ( = 0.002). No adverse effects were reported. The literature search showed similar results. Our data supports the concept that BTX-A is effective, well tolerated, and safe in adolescents with CM resistant to oral preventatives.
Topics: Humans; Migraine Disorders; Botulinum Toxins, Type A; Adolescent; Female; Male; Prospective Studies; Chronic Disease; Treatment Outcome; Neuromuscular Agents
PubMed: 38787073
DOI: 10.3390/toxins16050221 -
Journal of the American Medical... Jul 2024The Drug Burden Index (DBI) calculates a person's exposure to anticholinergic and sedative medications. We aimed to review randomized controlled trials (RCTs) of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The Drug Burden Index (DBI) calculates a person's exposure to anticholinergic and sedative medications. We aimed to review randomized controlled trials (RCTs) of deprescribing interventions that reported the DBI as an outcome, their characteristics, effectiveness in reducing the DBI, and impact on other outcomes.
DESIGN
Systematic review with meta-analysis.
SETTING AND PARTICIPANTS
RCTs of deprescribing interventions where the DBI was measured as a primary or secondary outcome in humans within any setting were included.
METHODS
Electronic databases, citation indexes, and gray literature were searched from April 1, 2007, to September 1, 2023. Quality was assessed using the Cochrane risk-of-bias tool.
RESULTS
Of 1721 records identified, 9 met the inclusion criteria. Six interventions were delivered by pharmacists and 3 were delivered by pharmacists/nurses or pharmacists/geriatricians. All interventions required at least intermediate-level skills and involved multiple components and target groups. Studies were conducted in the community (n = 5), nursing homes (n = 2), and hospitals (n = 2). The mean or median age was ≥75 years and most participants were women in all studies. Most (n = 6) studies were underpowered. The follow-up period ranged from 3 to 12 months. Three studies reported a lower DBI in the intervention group compared with control: 1 pharmacist independent prescriber-delivered in nursing homes (adjusted rate ratio, 0.83; 95% CI, 0.74 to 0.92), 1 pharmacist/nurse practitioner-delivered in hospital (adjusted mean difference (MD), -0.28; 95% CI, -0.51 to -0.04), and 1 geriatrician/pharmacist-delivered in hospital (MD, -0.28; 95% CI, -0.52 to -0.04). Meta-analysis showed no difference in the change in DBI between control and intervention groups in the community including nursing homes (MD, -0.03; 95% CI, -0.08 to 0.01) or hospital setting (MD, -0.19; 95% CI, -0.45 to 0.06). Interventions had inconsistent effects on cognition and no effect on other reported outcomes.
CONCLUSIONS AND IMPLICATIONS
RCTs of deprescribing interventions had no significant impact on reducing DBI or improving outcomes. Further suitably powered studies are required.
Topics: Humans; Deprescriptions; Randomized Controlled Trials as Topic; Aged; Hypnotics and Sedatives; Female; Male; Cholinergic Antagonists
PubMed: 38763161
DOI: 10.1016/j.jamda.2024.105021 -
Clinical Oral Investigations May 2024To investigate the effectiveness of botulinum toxin in the salivary glands of patients with neurological impairment and drooling and its impact on the quality of life.
OBJECTIVE
To investigate the effectiveness of botulinum toxin in the salivary glands of patients with neurological impairment and drooling and its impact on the quality of life.
MATERIALS AND METHODS
This systematic review was registered with the International Prospective Register of Systematic Reviews (CRD 42,023,435,242) and conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. An electronic search was performed in the PubMed/MEDLINE, Embase, Scopus, Cochrane Library, and clinical trial databases until August 2023, no language restriction. Cohort studies and randomized clinical trials of patients diagnosed with drooling and neurological impairment who used botulinum toxin on the salivary gland were included, which evaluated subjective quality of life parameters. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist and Risk of Bias 2 tools. The certainty of the evidence was analyzed using the Grading of Recommendations Assessment, Development, and Evaluation approach.
RESULTS
Eight studies involving 317 patients were included. All studies, through subjective parameters, suggested the effectiveness of botulinum toxin in reducing drooling, resulting in an improvement in the quality of life. Three studies demonstrated improvements in swallowing and four in cases of respiratory diseases. Two clinical trials had a high risk of bias, whereas one had low risk. The five cohort studies that were evaluated had a high risk of bias. The certainty of the evidence was considered low.
CONCLUSIONS
Based on the patient/caregivers' perception of improvement in drooling, dysphagia, and respiratory symptoms, it can be inferred that botulinum toxin application reduces subjective drooling in neurologically compromised patients. Its impact contributes to the general well-being and quality of life.
CLINICAL RELEVANCE
Injection of botulinum toxin into the salivary glands can be considered an alternative technique to surgical or medicinal approaches in reducing drooling. It is effective, less invasive and without significant side effects. It promotes a positive impact on the well-being and quality of life of neurological patients.
Topics: Humans; Botulinum Toxins; Botulinum Toxins, Type A; Nervous System Diseases; Neuromuscular Agents; Quality of Life; Sialorrhea
PubMed: 38758415
DOI: 10.1007/s00784-024-05718-y