-
CNS Drugs Mar 2019Clozapine is the most effective medication for treatment-refractory schizophrenia. However, it has a high burden of adverse events, including common adverse events such... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia. However, it has a high burden of adverse events, including common adverse events such as sialorrhea. Sialorrhea can lead to severe physical complications such as aspiration pneumonia, as well as psychological complications including embarrassment and low self-esteem. Compromised adherence and treatment discontinuation can occur due to intolerability. There have been no meta-analyses examining strategies to mitigate clozapine-induced sialorrhea.
METHODS
We systematically searched Chinese and Western research databases for randomised controlled trials examining agents for clozapine-induced sialorrhea. No limit to language or date were applied to the search. Where sufficient data for individual agents was available, pairwise meta-analyses were conducted. Results were provided as risk ratios and number needed to treat. Sensitivity analysis was conducted by study quality. Adverse events were provided as number needed to harm.
RESULTS
19 studies provided data for use in the meta-analysis. Improvement in clozapine-induced sialorrhea was seen in meta-analyses of propantheline (studies = 6, risk ratio [RR] 2.38, 95% confidence interval [CI] 1.52-3.73; number needed to treat [NNT] 3, 95% CI 1.9-2.7), diphenhydramine (studies = 5, RR 3.09, 95% CI 2.36-4.03; NNT 2, 95% CI 1.5-2.0), chlorpheniramine (studies = 2, RR 2.37, 95% CI 1.59-3.55; NNT 3, 95% CI 1.6-3.5), and benzamide derivatives (odds ratio [OR] 6.93, 95% CI 3.03-15.86). When meta-analyses were limited to high-quality studies, all these results remained significant. Single studies of benzhexol, cyproheptadine, doxepin and Kongyan Tang showed promise. Propantheline increased rates of constipation with a number needed to harm (NNH) of 9 (95% CI 4.2-204.1).
CONCLUSION
Clozapine-induced sialorrhea is a potentially serious adverse event. Included studies in this meta-analysis were limited by poor study quality. Diphenhydramine, chlorpheniramine and benzamide derivatives appear to have the best supporting evidence and lowest reported adverse events. Caution should be exercised when using propantheline given its increased risk of constipation.
Topics: Antidepressive Agents; Antipsychotic Agents; Clozapine; Histamine Antagonists; Humans; Medicine, Chinese Traditional; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Salivation; Schizophrenia; Sialorrhea
PubMed: 30758782
DOI: 10.1007/s40263-019-00612-8 -
Nederlands Tijdschrift Voor... Nov 2018Evidence-based reviews of drugs causing medication-induced salivary gland dysfunction, such as xerostomia (sensation of oral dryness) and subjective sialorrhea are...
Evidence-based reviews of drugs causing medication-induced salivary gland dysfunction, such as xerostomia (sensation of oral dryness) and subjective sialorrhea are lacking. To compile a list of medicaments that influence salivary gland function, electronic databases were searched for relevant articles published up to June 2013. A total of 269 papers out of 3,867 records located satisfied the inclusion criteria (relevance, quality of methodology, strength of evidence). A total of 56 active substances with a higher level of evidence and 50 active substances with a moderate level of evidence of causing salivary gland dysfunction are described in this article. While xerostomia was a commonly reported outcome, the objective effect on salivary secretion was rarely measured. Xerostomia was, moreover, mostly reported as a negative side effect instead of the intended effect of that drug. A comprehensive list of medications having documented effects on salivary gland function or symptoms was compiled, which may assist practitioners in assessing patients who complain of dry mouth while taking medications.
Topics: Humans; Salivary Glands; Xerostomia
PubMed: 30457580
DOI: 10.5177/ntvt.2018.11.18203 -
Developmental Medicine and Child... Jan 2019To review the evidence for behavioural interventions to reduce drooling in children with neurodisability.
AIM
To review the evidence for behavioural interventions to reduce drooling in children with neurodisability.
METHOD
A detailed search in eight databases sought studies that: (1) included participants aged 0 to 18 years with neurodisability and drooling; (2) provided behavioural interventions targeting drooling or a drooling-related behaviour; and (3) used experimental designs. Two reviewers extracted data from full-text papers independently. Results were tabulated for comparison. The Risk of Bias assessment in N-of-1 Trials scale for single case experimental designs (SCEDs) and the Cochrane risk of bias assessment tool for randomized controlled trials (RCTs) were applied.
RESULTS
Of an initial yield of 763, seven SCEDs and one RCT were included. Behavioural interventions included the use of reinforcement, prompting, self-management, instruction, extinction, overcorrection, and fading. Each assessed body functions or structures' outcomes (drooling frequency and severity); three included activity outcomes (mouth drying, head control, eye contact, and vocalizations) and none assessed participation or quality of life. While each study reported positive effects of intervention, risk of bias was high.
INTERPRETATION
Low-level evidence suggests behavioural interventions may be useful for treatment of drooling in children with neurodisability. Well-designed intervention studies are urgently needed to determine effectiveness.
WHAT THIS PAPER ADDS
Behavioural interventions used to treat drooling included reinforcement, prompting, self-management, extinction, overcorrection, instruction, and fading. Interventions targeted body structures and function-level outcomes and activity-level outcomes. Low-level evidence supports the use of behavioural intervention to treat drooling.
Topics: Adolescent; Behavior Therapy; Child; Child, Preschool; Humans; Infant; Neurodevelopmental Disorders; Sialorrhea
PubMed: 30276810
DOI: 10.1111/dmcn.14048 -
JAMA Otolaryngology-- Head & Neck... Aug 2018Complex head and neck cancer defects that require multiflap reconstructions are technically feasible, but the morbidity and patient outcomes of such large-scale head and...
IMPORTANCE
Complex head and neck cancer defects that require multiflap reconstructions are technically feasible, but the morbidity and patient outcomes of such large-scale head and neck operations have yet to be systematically reviewed.
OBJECTIVE
To systematically review existing literature to characterize the outcomes of large-scale head and neck resections that require multiple-flap reconstructions (defined as defects that require >1 flap [free, pedicled, or combinations thereof]).
EVIDENCE REVIEW
Two authors independently searched PubMed, Embase, and the Cochrane Review databases for English-only texts published on any date. Included studies examined patients who underwent complex head and neck surgical resections that required multiple simultaneous flaps for reconstruction. Included studies reported results on at least one of the following outcomes: functional and aesthetic, patient survival, or cost (estimated by operating room time, length of stay, and/or complications). Methodological Index for Non-Randomized Studies (MINORS) criteria for bias and modified Oxford Centre for Evidence-Based Medicine recommendations were used to assess study quality.
FINDINGS
Twenty-four studies published from November 1, 1992, through September 1, 2016, met the final inclusion criteria, with a total of 487 patients (370 male [79.4%]; mean [SD] weighted age, 55.1 [4.1] years). Sixty-two of 250 patients (24.8%) were partially or fully dependent on feeding tubes at follow-up. Twenty-two of 75 patients (29.3%) had poor postoperative oral competence, causing moderate to severe drooling. Nineteen of 108 patients (17.6%) had unintelligible speech. Nine of 64 patients (14.1%) were unsatisfied with their aesthetic outcome. The mean (SD) reported survival was 2.36 (1.39) years. The mean (SD) length of stay was 24.5 (12.2) days in 219 patients. Eighty-eight minor complications (eg, partial flap necrosis, donor site complications) and 185 major complications (eg, surgical reexplorations, flap loss, or cardiopulmonary complications) were reported in 380 patients. Mean (SD) MINORS scores were 16.0 (3.2) for comparison studies and 11.4 (1.8) for noncomparison studies.
CONCLUSIONS AND RELEVANCE
Because of limited patient life expectancies, modest functional and aesthetic outcomes, and significant associated costs, surgeons should weigh the curative potential and palliative benefits for individual patients with a comprehensive view of the overall outcomes of extensive head and neck resections and reconstructions. Realistic expectations should be emphasized during preoperative discussions with patients.
Topics: Head and Neck Neoplasms; Humans; Plastic Surgery Procedures; Surgical Flaps; Treatment Outcome
PubMed: 29978196
DOI: 10.1001/jamaoto.2018.0835 -
Obesity Surgery Oct 2018Laparoscopic greater curvature plication (LGP) has recently emerged as a new bariatric procedure. This surgery provides gastric restriction without resection, which... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Laparoscopic greater curvature plication (LGP) has recently emerged as a new bariatric procedure. This surgery provides gastric restriction without resection, which could potentially provide a lower risk alternative, with fewer complications. The real benefit of this technique in the short and long term is unknown. This systematic review aims to compare laparoscopic gastric plication and laparoscopic sleeve gastrectomy for obesity treatment.
METHODS
Clinical trials were identified in MEDLINE, Embase, Cochrane, LILACS, BVS, SCOPUS, and CINAHL databases. Comparison of LGP and laparoscopic sleeve gastrectomy (SG) included hospital stay, operative time, loss of hunger feeling, body mass index loss (BMIL), percentage of excess weight loss (%EWL), complications, symptoms in the postoperative period, and comorbidity remission or improvement.
RESULTS
This systematic review search included 17,423 records. Eight studies were selected for meta-analysis. There is no difference in operative time, hospital stay, and complications. Patients in the SG group had improved loss of hunger feeling. BMIL was better in the SG group at 12 and 24 months [mean difference (MD) - 2.19, 95% confidence interval (CI) - 3.10 to - 1.28, and MD - 4.59, 95% CI - 5.55 to - 3.63, respectively]. SG showed improved %EWL compared with gastric plication in 3, 6, 12, and 24 months. However, no difference was found in %EWL long-term results (24 and 36 months). Patients who underwent LGP had more sialorrhea. SG showed better results in diabetes remission.
CONCLUSIONS
SG showed improved weight loss when compared with LGP, with better satiety, fewer symptoms in the postoperative period, and improved diabetes remission.
Topics: Bariatric Surgery; Gastrectomy; Humans; Laparoscopy; Length of Stay; Obesity, Morbid; Operative Time; Postoperative Complications; Treatment Outcome; Weight Loss
PubMed: 29951784
DOI: 10.1007/s11695-018-3330-9 -
International Journal of Environmental... May 2018The collection of salivary cortisol has been chosen as one of the least intrusive, easiest to collect, analyze, and store methods of obtaining information on...
The collection of salivary cortisol has been chosen as one of the least intrusive, easiest to collect, analyze, and store methods of obtaining information on physiological changes. It is, however, not clear what the best practice is when collecting salivary cortisol from children within the school setting. The aim of this systematic review is to evaluate the feasibility of cortisol collection in schools for future research and to make recommendations for best practice. The review included 25 peer-reviewed articles from seven databases. The hypotheses of the included studies vary, but they all use cortisol as a diurnal, baseline, or acute measure, or to measure the effect of an intervention. Two methods of salivary cortisol collection were preferred by most of the research, i.e., passive drool or cotton Salivettes. The review has concluded that cortisol is a physiological marker that can be successfully measured in school-based research. However, there are discrepancies across studies when evaluating the collection guidelines, protocols, and instructions to participants as well as transparency of the success rate of obtaining all samples. Recommendations are made for future research to address and avoid such discrepancies and improve cross-study comparisons by implementing standard protocol guidelines.
Topics: Child; Humans; Hydrocortisone; Saliva; Schools; Specimen Handling
PubMed: 29783677
DOI: 10.3390/ijerph15051025 -
Journal of Clinical Neuroscience :... May 2018Sialorrhea is a common distress associated with certain neurological disorders. The aim of this study is to compare the pharmacological agents used for treating... (Meta-Analysis)
Meta-Analysis Review
Sialorrhea is a common distress associated with certain neurological disorders. The aim of this study is to compare the pharmacological agents used for treating sialorrhea by network meta-analysis. Electronic databases were searched for randomized clinical trials comparing active drugs with either placebo or other active drugs. Total drooling scores was the primary outcome measure. Inverse variance heterogeneity model was used for both direct and mixed treatment comparison analysis. Twenty one studies were included in the systematic review and 15 in the meta-analysis. Compared to placebo, benztropine, botulinum toxins A and B are associated with a significant reduction in the frequency and severity of drooling both in the overall neurological disorders as well as for children with cerebral palsy. Only botulinum toxin A and B were associated with significant therapeutic effects in Parkinson's disease. Benztropine and botulinum toxins A and B were observed to be effective in reducing sialorrhea associated with neurological disorders.
Topics: Benztropine; Botulinum Toxins, Type A; Child; Child, Preschool; Female; Glycopyrrolate; Humans; Muscarinic Antagonists; Nervous System Diseases; Network Meta-Analysis; Randomized Controlled Trials as Topic; Scopolamine; Sialorrhea
PubMed: 29475576
DOI: 10.1016/j.jocn.2018.02.011 -
Journal of Clinical Movement Disorders 2017The aim of this study was to examine the efficacy, safety and dosing practices of rimabotulinumtoxinB (BoNT-B) for the treatment of patients with sialorrhea based on a... (Review)
Review
OBJECTIVE
The aim of this study was to examine the efficacy, safety and dosing practices of rimabotulinumtoxinB (BoNT-B) for the treatment of patients with sialorrhea based on a systematic review of clinical trials.
METHODS
A systematic literature review was performed to identify randomized controlled trials and other comparative clinical studies of BoNT-B for the treatment of sialorrhea published in English between January 1999 and December 2015. Medical literature databases (PubMed, Cochrane Library, and EMBASE) were searched and a total of 41 records were identified. Of these, six primary publications that evaluated BoNT-B for the treatment of sialorrhea met criteria and were included in the final data report.
SYNTHESIS
Total BoNT-B doses ranged from 1500 to 4000 units for sialorrhea. Most of the studies in sialorrhea showed statistically significant benefits of BoNT-B versus placebo (range 4-19.2 weeks). BoNT-B was generally well tolerated across the individual studies; most adverse events reported were considered unrelated to treatment. Adverse events considered potentially associated with BoNT-B included: dry mouth, change in saliva thickness, mild transient dysphagia, mild weakness of chewing and diarrhea.
CONCLUSIONS
BoNT-B significantly reduces sialorrhea at doses between 1500 and 4000 units. The relatively mild dose-dependent adverse events suggest both direct and remote toxin effects.
PubMed: 28593050
DOI: 10.1186/s40734-017-0055-1 -
What sleep behaviors are associated with bruxism in children? A systematic review and meta-analysis.Sleep & Breathing = Schlaf & Atmung Dec 2017The aim of this article was to assess the sleep behaviors that serve as risk factors related to bruxism in children ages 0 to 12 years by performing a systematic review... (Meta-Analysis)
Meta-Analysis
PURPOSE
The aim of this article was to assess the sleep behaviors that serve as risk factors related to bruxism in children ages 0 to 12 years by performing a systematic review and meta-analysis of published studies.
METHODS
Seven databases were searched to identify all peer-reviewed articles potentially relevant to the review. Data were pooled for random-effects modeling. Sleep risk factors related to bruxism in this age group are summarized using pooled odds ratios (ORs), 95% confidence intervals (CIs), and P values.
RESULTS
Of 5637 initially identified articles, 14 met inclusion criteria. Study qualities of all case-control studies were high. Quality of cross-sectional studies was more variable. The pooled ORs, 95% CIs, and P values were as follows: snoring (2.86, 1.85-4.42, <0.0001), mouth breathing (1.51, 1.04-2.18, 0.029), restless sleep (2.31, 1.89-2.83, <0.0001), drooling (1.79, 1.07-2.97, 0.026), stomach position during sleep (1.70, 1.0-2.39, 0.003), and inadequate sleep time (2.56, 1.48-4.43, 0.001).
CONCLUSIONS
Snoring, mouth breathing, restless sleep, drooling, stomach position during sleep, and lack of sleep were the risk factors related to bruxism in children.
Topics: Case-Control Studies; Child; Cohort Studies; Cross-Sectional Studies; Humans; Sleep; Sleep Bruxism; Snoring
PubMed: 28396971
DOI: 10.1007/s11325-017-1496-3 -
The Cochrane Database of Systematic... Jan 2017Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of... (Review)
Review
BACKGROUND
Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of the symptomatic treatment therapies is limited.
OBJECTIVES
To summarise the evidence from Cochrane Systematic Reviews of all symptomatic treatments for MND.
METHODS
We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 November 2016 for systematic reviews of symptomatic treatments for MND. We assessed the methodological quality of the included reviews using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the GRADE approach. We followed standard Cochrane study (review) selection and data extraction procedures. We reported findings narratively and in tables.
MAIN RESULTS
We included nine Cochrane Systematic Reviews of interventions to treat symptoms in people with MND. Three were empty reviews with no included randomised controlled trials (RCTs); however, all three reported on non-RCT evidence and the remaining six included mostly one or two studies. We deemed all of the included reviews of high methodological quality. Drug therapy for painThere is no RCT evidence in a Cochrane Systematic Review exploring the efficacy of drug therapy for pain in MND. Treatment for crampsThere is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate-quality evidence);- vitamin E may have little or no effect (low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data.The review reported adverse effects of riluzole, but it is not clear whether other interventions had adverse effects. Treatment for spasticityIt is uncertain whether an endurance-based exercise programme improved spasticity or quality of life, measured at three months after the programme, as the quality of evidence is very low (1 RCT, comparison "usual activities", N = 25). The review did not evaluate other approaches, such as use of baclofen as no RCTs were available. Mechanical ventilation for supporting respiratory functionNon-invasive ventilation (NIV) probably improves median survival and quality of life in people with respiratory insufficiency and normal to moderately impaired bulbar function compared to standard care, and improves quality of life but not survival for people with poor bulbar function (1 RCT, N = 41, moderate-quality evidence; a second RCT did not provide data). The review did not evaluate other approaches such as tracheostomy-assisted ('invasive') ventilation, or assess timing of NIV initiation. Treatment for sialorrhoeaA single session of botulinum toxin type B injections to parotid and submandibular glands probably improves sialorrhoea and quality of life at up to 4 weeks compared to placebo injections, but not at 8 or 12 weeks after the injections (moderate-quality evidence from 1 placebo-controlled RCT, N = 20). The review authors found no trials of other approaches. Enteral tube feeding for supporting nutritionThere is no RCT evidence in a Cochrane Systematic Review to support benefit or harms of enteral tube feeding in supporting nutrition in MND. Repetitive transcranial magnetic stimulationIt is uncertain whether repetitive transcranial magnetic stimulation (rTMS) improves disability or limitation in activity in MND in comparison with sham rTMS (3 RCTs, very low quality evidence, N = 50). Therapeutic exerciseThere is evidence that exercise may improve disability in MND at three months after the exercise programme, but not quality of life, in comparison with "usual activities" or "usual care" including stretching (2 RCTs, low-quality evidence, N = 43). Multidisciplinary careThere is no RCT evidence in a Cochrane Systematic Review to demonstrate any benefit or harm for multidisciplinary care in MND.None of the reviews, other than the review of treatment for cramps, reported that adverse events occurred. However, the trials were too small for reliable adverse event reporting.
AUTHORS' CONCLUSIONS
This overview has highlighted the lack of robust evidence in Cochrane Systematic Reviews on interventions to manage symptoms resulting from MND. It is important to recognise that clinical trials may fail to demonstrate efficacy of an intervention for reasons other than a true lack of efficacy, for example because of insufficient statistical power, the wrong choice of dose, insensitive outcome measures or inappropriate participant eligibility. The trials were mostly too small to reliably assess adverse effects of the treatments. The nature of MND makes it difficult to research clinically accepted or recommended practice, regardless of the level of evidence supporting the practice. It would not be ethical, for example, to design a placebo-controlled trial for treatment of pain in MND or to withhold multidisciplinary care where such care is available. It is therefore highly unlikely that there will ever be classically designed placebo-controlled RCTs in these areas.We need more research with appropriate study designs, robust methodology, and of sufficient duration to address the changing needs-of people with MND and their caregivers-associated with MND disease progression and mortality. There is a significant gap in studies assessing the effectiveness of interventions for symptoms relating to MND, such as pseudobulbar emotional lability and cognitive and behavioural difficulties. Future studies should use appropriate outcome measures that are reliable, have internal and external validity, and are sensitive to change in what is being measured (such as quality of life).
Topics: Amyotrophic Lateral Sclerosis; Enteral Nutrition; Exercise Therapy; Humans; Motor Neuron Disease; Muscle Cramp; Muscle Spasticity; Noninvasive Ventilation; Pain; Respiratory Insufficiency; Review Literature as Topic; Sialorrhea; Transcranial Magnetic Stimulation
PubMed: 28072907
DOI: 10.1002/14651858.CD011776.pub2