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World Journal of Gastroenterology Mar 2015To investigate the efficacy of probiotics in irritable bowel syndrome (IBS) patients. (Meta-Analysis)
Meta-Analysis Review
AIM
To investigate the efficacy of probiotics in irritable bowel syndrome (IBS) patients.
METHODS
PubMed, Cochrane library, Scopus, Google Scholar, and Clinicaltrial.gov databases were searched for literature published between September 2007 and December 2013. The applied Mesh terms were "probiotics," "irritable bowel syndrome," and "irritable bowel syndrome treatment." The collected data contained24 clinical trials, of which 15 were eligible for meta-analysis and nine were reviewed systematically. All studies were randomized placebo-controlled trials in patients with IBS that investigated the efficacy of probiotics in IBS improvement. The Jadad score was used to assess the methodological quality of trials. The quality scale ranges from 0 to 5 points, with a score ≤ 2 indicating a low quality report, and a score of ≥ 3 indicating a high quality report. Relative risk (RR), standardized effect size, and 95%CI were calculated using the DerSimonian-Laird method. The Cochran Q test was used to test heterogeneity with P < 0.05. Funnel plots were constructed and Egger's and Begg-Mazumdar tests were performed to assess publication bias.
RESULTS
A total of 1793 patients were included in the meta-analysis. The RR of responders to therapies based on abdominal pain score in IBS patients for two included trials comparing probiotics to placebo was 1.96 (95%CI: 1.14-3.36; P = 0.01). RR of responders to therapies based on a global symptom score in IBS patients for two included trials comparing probiotics with placebo was 2.43 (95%CI: 1.13-5.21; P = 0.02). For adequate improvement of general symptoms in IBS patients, the RR of seven included trials (six studies) comparing probiotics with placebo was 2.14 (95%CI: 1.08-4.26; P = 0.03). Distension, bloating, and flatulence were evaluated using an IBS severity scoring system in three trials (two studies) to compare the effect of probiotic therapy in IBS patients with placebo, the standardized effect size of mean differences for probiotics therapy was -2.57 (95%CI: -13.05--7.92).
CONCLUSION
Probiotics reduce pain and symptom severity scores. The results demonstrate the beneficial effects of probiotics in IBS patients in comparison with placebo.
Topics: Abdominal Pain; Flatulence; Humans; Intestines; Irritable Bowel Syndrome; Odds Ratio; Pain Measurement; Probiotics; Quality of Life; Recovery of Function; Severity of Illness Index; Treatment Outcome
PubMed: 25780308
DOI: 10.3748/wjg.v21.i10.3072 -
The Cochrane Database of Systematic... Nov 2022Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite... (Review)
Review
BACKGROUND
Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite the fact that medication use is off-label as a treatment for BPD. Nevertheless, people with BPD often receive several psychotropic drugs at a time for sustained periods.
OBJECTIVES
To assess the effects of pharmacological treatment for people with BPD.
SEARCH METHODS
For this update, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers up to February 2022. We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals. We did not restrict the search by year of publication, language or type of publication.
SELECTION CRITERIA
Randomised controlled trials comparing pharmacological treatment to placebo, other pharmacologic treatments or a combination of pharmacologic treatments in people of all ages with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self-harm, suicide-related outcomes, and psychosocial functioning. Secondary outcomes were individual BPD symptoms, depression, attrition and adverse events.
DATA COLLECTION AND ANALYSIS
At least two review authors independently selected trials, extracted data, assessed risk of bias using Cochrane's risk of bias tool and assessed the certainty of the evidence using the GRADE approach. We performed data analysis using Review Manager 5 and quantified the statistical reliability of the data using Trial Sequential Analysis.
MAIN RESULTS
We included 46 randomised controlled trials (2769 participants) in this review, 45 of which were eligible for quantitative analysis and comprised 2752 participants with BPD in total. This is 18 more trials than the 2010 review on this topic. Participants were predominantly female except for one trial that included men only. The mean age ranged from 16.2 to 39.7 years across the included trials. Twenty-nine different types of medications compared to placebo or other medications were included in the analyses. Seventeen trials were funded or partially funded by the pharmaceutical industry, 10 were funded by universities or research foundations, eight received no funding, and 11 had unclear funding. For all reported effect sizes, negative effect estimates indicate beneficial effects by active medication. Compared with placebo, no difference in effects were observed on any of the primary outcomes at the end of treatment for any medication. Compared with placebo, medication may have little to no effect on BPD symptom severity, although the evidence is of very low certainty (antipsychotics: SMD -0.18, 95% confidence interval (CI) -0.45 to 0.08; 8 trials, 951 participants; antidepressants: SMD -0.27, 95% CI -0.65 to 1.18; 2 trials, 87 participants; mood stabilisers: SMD -0.07, 95% CI -0.43 to 0.57; 4 trials, 265 participants). The evidence is very uncertain about the effect of medication compared with placebo on self-harm, indicating little to no effect (antipsychotics: RR 0.66, 95% CI 0.15 to 2.84; 2 trials, 76 participants; antidepressants: MD 0.45 points on the Overt Aggression Scale-Modified-Self-Injury item (0-5 points), 95% CI -10.55 to 11.45; 1 trial, 20 participants; mood stabilisers: RR 1.08, 95% CI 0.79 to 1.48; 1 trial, 276 participants). The evidence is also very uncertain about the effect of medication compared with placebo on suicide-related outcomes, with little to no effect (antipsychotics: SMD 0.05, 95 % CI -0.18 to 0.29; 7 trials, 854 participants; antidepressants: SMD -0.26, 95% CI -1.62 to 1.09; 2 trials, 45 participants; mood stabilisers: SMD -0.36, 95% CI -1.96 to 1.25; 2 trials, 44 participants). Very low-certainty evidence shows little to no difference between medication and placebo on psychosocial functioning (antipsychotics: SMD -0.16, 95% CI -0.33 to 0.00; 7 trials, 904 participants; antidepressants: SMD -0.25, 95% CI -0.57 to 0.06; 4 trials, 161 participants; mood stabilisers: SMD -0.01, 95% CI -0.28 to 0.26; 2 trials, 214 participants). Low-certainty evidence suggests that antipsychotics may slightly reduce interpersonal problems (SMD -0.21, 95% CI -0.34 to -0.08; 8 trials, 907 participants), and that mood stabilisers may result in a reduction in this outcome (SMD -0.58, 95% CI -1.14 to -0.02; 4 trials, 300 participants). Antidepressants may have little to no effect on interpersonal problems, but the corresponding evidence is very uncertain (SMD -0.07, 95% CI -0.69 to 0.55; 2 trials, 119 participants). The evidence is very uncertain about dropout rates compared with placebo by antipsychotics (RR 1.11, 95% CI 0.89 to 1.38; 13 trials, 1216 participants). Low-certainty evidence suggests there may be no difference in dropout rates between antidepressants (RR 1.07, 95% CI 0.65 to 1.76; 6 trials, 289 participants) and mood stabilisers (RR 0.89, 95% CI 0.69 to 1.15; 9 trials, 530 participants), compared to placebo. Reporting on adverse events was poor and mostly non-standardised. The available evidence on non-serious adverse events was of very low certainty for antipsychotics (RR 1.07, 95% CI 0.90 to 1.29; 5 trials, 814 participants) and mood stabilisers (RR 0.84, 95% CI 0.70 to 1.01; 1 trial, 276 participants). For antidepressants, no data on adverse events were identified.
AUTHORS' CONCLUSIONS
This review included 18 more trials than the 2010 version, so larger meta-analyses with more statistical power were feasible. We found mostly very low-certainty evidence that medication may result in no difference in any primary outcome. The rest of the secondary outcomes were inconclusive. Very limited data were available for serious adverse events. The review supports the continued understanding that no pharmacological therapy seems effective in specifically treating BPD pathology. More research is needed to understand the underlying pathophysiologic mechanisms of BPD better. Also, more trials including comorbidities such as trauma-related disorders, major depression, substance use disorders, or eating disorders are needed. Additionally, more focus should be put on male and adolescent samples.
Topics: Humans; Adolescent; Male; Female; Young Adult; Adult; Borderline Personality Disorder; Reproducibility of Results; Antidepressive Agents; Depressive Disorder, Major; Antipsychotic Agents
PubMed: 36375174
DOI: 10.1002/14651858.CD012956.pub2 -
The Cochrane Database of Systematic... Oct 2016Many treatments for the common cold exist and are sold over-the-counter. Nevertheless, evidence on the effectiveness and safety of nasal decongestants is limited. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many treatments for the common cold exist and are sold over-the-counter. Nevertheless, evidence on the effectiveness and safety of nasal decongestants is limited.
OBJECTIVES
To assess the efficacy, and short- and long-term safety, of nasal decongestants used in monotherapy to alleviate symptoms of the common cold in adults and children.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 6, June 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Specialised Register, MEDLINE (1946 to July 2016), Embase (2010 to 15 July 2016), CINAHL (1981 to 15 July 2016), LILACS (1982 to July 2016), Web of Science (1955 to July 2016) and clinical trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and cluster-RCTs investigating the effectiveness and adverse effects of nasal decongestants compared with placebo for treating the common cold in adults and children. We excluded quasi-RCTs.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted and summarised data on subjective measures of nasal congestion, overall patient well-being score, objective measures of nasal airway resistance, adverse effects and general recovery. One review author acted as arbiter in cases of disagreement. We categorised trials as single and multi-dose and analysed data both separately and together. We also analysed studies using an oral or topical nasal decongestant separately and together.
MAIN RESULTS
We included 15 trials with 1838 participants. Fourteen studies included adult participants only (aged 18 years and over). In six studies the intervention was a single dose and in nine studies multiple doses were used. Nine studies used pseudoephedrine and three studies used oxymetazoline. Other decongestants included phenylpropanolamine, norephedrine and xylometazoline. Phenylpropanolamine (or norephedrine) is no longer available on the market therefore we did not include the results of these studies in the meta-analyses. Eleven studies used oral decongestants; four studies used topical decongestants.Participants were included after contracting the common cold. The duration of symptoms differed among studies; in 10 studies participants had symptoms for less than three days, in three studies symptoms were present for less than five days, one study counted the number of colds over one year, and one study experimentally induced the common cold. In the single-dose studies, the effectiveness of a nasal decongestant was measured on the same day, whereas the follow-up in multi-dose studies ranged between one and 10 days.Most studies were conducted in university settings (N = eight), six at a specific university common cold centre. Three studies were conducted at a university in collaboration with a hospital and two in a hospital only setting. In two studies the setting was unclear.There were large differences in the reporting of outcomes and the reporting of methods in most studies was limited. Therefore, we judged most studies to be at low or unclear risk of bias. Pooling was possible for a limited number of studies only; measures of effect are expressed as standardised mean differences (SMDs). A positive SMD represents an improvement in congestion. There is no defined minimal clinically important difference for measures of subjective improvement in nasal congestion, therefore we used the SMDs as a guide to assess whether an effect was small (0.2 to 0.49), moderate (0.5 to 0.79) or large (≥ 0.8).Single-dose decongestant versus placebo: 10 studies compared a single dose of nasal decongestant with placebo and their effectiveness was tested between 15 minutes and 10 hours after dosing. Seven of 10 studies reported subjective symptom scores for nasal congestion; none reported overall patient well-being. However, pooling was not possible due to the large diversity in the measurement and reporting of symptoms of congestion. Two studies recorded adverse events. Both studies used an oral decongestant and each of them showed that there was no statistical difference between the number of adverse events in the treatment group versus the placebo group.Multi-dose decongestant versus placebo: nine studies compared multiple doses of nasal decongestants with placebo, but only five reported on the primary outcome, subjective symptom scores for nasal congestion. Only one study used a topical decongestant; none reported overall patient well-being. Subjective measures of congestion were significantly better for the treatment group compared with placebo approximately three hours after the last dose (SMD 0.49, 95% confidence interval (CI) 0.07 to 0.92; P = 0.02; GRADE: low-quality evidence). However, the SMD of 0.49 only indicates a small clinical effect. Pooling was based on two studies, one oral and one topical, therefore we were unable to assess the effects of oral and topical decongestants separately. Seven studies reported adverse events (six oral and one topical decongestant); meta-analysis showed that there was no statistical difference between the number of adverse events in the treatment group (125 per 1000) compared to the placebo group (126 per 1000). The odds ratio (OR) for adverse events in the treatment group was 0.98 (95% CI 0.68 to 1.40; P = 0.90; GRADE: low-quality evidence). The results remained the same when we only considered studies using an oral decongestant (OR 0.95, 95% CI 0.65 to 1.39; P = 0.80; GRADE: low-quality evidence).
AUTHORS' CONCLUSIONS
We were unable to draw conclusions on the effectiveness of single-dose nasal decongestants due to the limited evidence available. For multiple doses of nasal decongestants, the current evidence suggests that these may have a small positive effect on subjective measures of nasal congestion in adults with the common cold. However, the clinical relevance of this small effect is unknown and there is insufficient good-quality evidence to draw any firm conclusions. Due to the small number of studies that used a topical nasal decongestant, we were also unable to draw conclusions on the effectiveness of oral versus topical decongestants. Nasal decongestants do not seem to increase the risk of adverse events in adults in the short term. The effectiveness and safety of nasal decongestants in children and the clinical relevance of their small effect in adults is yet to be determined.
Topics: Administration, Intranasal; Adult; Child; Common Cold; Humans; Imidazoles; Nasal Decongestants; Oxymetazoline; Phenylpropanolamine; Pseudoephedrine; Randomized Controlled Trials as Topic; Time Factors
PubMed: 27748955
DOI: 10.1002/14651858.CD009612.pub2 -
Climacteric : the Journal of the... Apr 2015To perform a meta-analysis examining the efficacy of phytoestrogens for the relief of menopausal symptoms. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To perform a meta-analysis examining the efficacy of phytoestrogens for the relief of menopausal symptoms.
METHODS
Medline, Cochrane, EMBASE, and Google Scholar databases were searched until September 30, 2013 using the following key words: vasomotor symptoms, menopausal symptoms, phytoestrogens, isoflavones, coumestrol, soy, red clover. Inclusion criteria were (1) randomized controlled trial (RCT), (2) perimenopausal or postmenopausal women experiencing menopausal symptoms, (3) intervention with an oral phytoestrogen. Outcome measures included Kupperman index (KI) changes, daily hot flush frequency, and the likelihood of side-effects.
RESULTS
Of 543 potentially relevant studies identified, 15 RCTs meeting the inclusion criteria were included. The mean age of the subjects ranged from 49 to 58.3 and 48 to 60.1 years, respectively, in the placebo and phytoestrogen groups. The number of participants ranged from 30 to 252, and the intervention periods ranged from 3 to 12 months. Meta-analysis of the seven studies that reported KI data indicated no significant treatment effect of phytoestrogen as compared to placebo (pooled mean difference = 6.44, p = 0.110). Meta-analysis of the ten studies that reported hot flush data indicated that phytoestrogens result in a significantly greater reduction in hot flush frequency compared to placebo (pooled mean difference = 0.89, p < 0.005). Meta-analysis of the five studies that reported side-effect data showed no significant difference between the two groups (p = 0.175).
CONCLUSION
Phytoestrogens appear to reduce the frequency of hot flushes in menopausal women, without serious side-effects.
Topics: Female; Hot Flashes; Humans; Isoflavones; Menopause; Middle Aged; Phytoestrogens; Phytotherapy; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25263312
DOI: 10.3109/13697137.2014.966241 -
International Journal of Environmental... Dec 2022Nightmares are highly prevalent and distressing for the sufferer, which underlines the need for well-documented treatments. A comprehensive literature review and... (Meta-Analysis)
Meta-Analysis Review
Nightmares are highly prevalent and distressing for the sufferer, which underlines the need for well-documented treatments. A comprehensive literature review and meta-analysis of the effects of different pharmacological placebo-controlled randomized clinical trials, covering the period up to 1 December 2022, was performed. Searches were conducted in PubMed, Embase, Web of Science, PsychInfo, Cinahl, and Google Scholar, resulting in the identification of 1762 articles, of which 14 met the inclusion criteria: pharmacological intervention of nightmares, based on a placebo-controlled randomized trial published in a European language, reporting outcomes either/or in terms of nightmare frequency, nightmare distress, or nightmare intensity, and reporting sufficient information enabling calculation of effect sizes. Most studies involved the effect of the α-adrenergic antagonist prazosin in samples of veterans or soldiers suffering from posttraumatic stress disorder. Other medications used were hydroxyzine, clonazepam, cyproheptadine, nabilone, and doxazosin. The vast majority of studies were conducted in the USA. The studies comprised a total of 830 participants. The Clinician-Administered PTSD Scale was the most frequently used outcome measure. The results showed an overall effect size of Hedges' = 0.50 (0.42 after adjustment for publication bias). The synthetic cannabinoid nabilone (one study) showed the highest effect size ( = 1.86), followed by the histamine H-antagonist hydroxyzine (one study), and prazosin (10 studies), with effect sizes of = 1.17 and = 0.54, respectively. Findings and limitations are discussed, and recommendations for future studies are provided.
Topics: Humans; Dreams; Randomized Controlled Trials as Topic; Prazosin; Adrenergic alpha-1 Receptor Antagonists; Stress Disorders, Post-Traumatic; Hydroxyzine
PubMed: 36613097
DOI: 10.3390/ijerph20010777 -
The Cochrane Database of Systematic... Jan 2022Although combination formulas containing antihistamines, decongestants, and/or analgesics are sold over-the-counter in large quantities for the common cold, the evidence... (Review)
Review
BACKGROUND
Although combination formulas containing antihistamines, decongestants, and/or analgesics are sold over-the-counter in large quantities for the common cold, the evidence for their effectiveness is limited. This is an update of a review first published in 2012.
OBJECTIVES
To assess the effectiveness of antihistamine-decongestant-analgesic combinations compared with placebo or other active controls (excluding antibiotics) in reducing the duration of symptoms and alleviating symptoms (general feeling of illness, nasal congestion, rhinorrhoea, sneezing, and cough) in children and adults with the common cold.
SEARCH METHODS
We searched CENTRAL, MEDLINE via EBSCOhost, Embase, CINAHL via EBSCOhost, LILACS, and Web of Science to 10 June 2021. We searched the WHO ICTRP and ClinicalTrials.gov on 10 June 2021.
SELECTION CRITERIA
Randomised controlled trials investigating the effectiveness of antihistamine-decongestant-analgesic combinations compared with placebo, other active treatment (excluding antibiotics), or no treatment in children and adults with the common cold.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. We categorised the included trials according to the active ingredients.
MAIN RESULTS
We identified 30 studies (6304 participants) including 31 treatment comparisons. The control intervention was placebo in 26 trials and an active substance (paracetamol, chlorphenindione + phenylpropanolamine + belladonna, diphenhydramine) in six trials (two trials had placebo as well as active treatment arms). Reporting of methods was generally poor, and there were large differences in study design, participants, interventions, and outcomes. Most of the included trials involved adult participants. Children were included in nine trials. Three trials included very young children (from six months to five years), and five trials included children aged 2 to 16. One trial included adults and children aged 12 years or older. The trials took place in different settings: university clinics, paediatric departments, family medicine departments, and general practice surgeries. Antihistamine-decongestant: 14 trials (1298 participants). Eight trials reported on global effectiveness, of which six studies were pooled (281 participants on active treatment and 284 participants on placebo). The odds ratio (OR) of treatment failure was 0.31 (95% confidence interval (CI) 0.20 to 0.48; moderate certainty evidence); number needed to treat for an additional beneficial outcome (NNTB) 3.9 (95% CI 3.03 to 5.2). On the final evaluation day (follow-up: 3 to 10 days), 55% of participants in the placebo group had a favourable response compared to 70% on active treatment. Of the two trials not pooled, one showed some global effect, whilst the other showed no effect. Adverse effects: the antihistamine-decongestant group experienced more adverse effects than the control group: 128/419 (31%) versus 100/423 (13%) participants suffered one or more adverse effects (OR 1.58, 95%CI 0.78 to 3.21; moderate certainty of evidence). Antihistamine-analgesic: four trials (1608 participants). Two trials reported on global effectiveness; data from one trial were presented (290 participants on active treatment and 292 participants on ascorbic acid). The OR of treatment failure was 0.33 (95% CI 0.23 to 0.46; moderate certainty evidence); NNTB 6.67 (95% CI 4.76 to 12.5). Forty-three per cent of participants in the control group and 70% in the active treatment group were cured after six days of treatment. The second trial also showed an effect in favour of the active treatment. Adverse effects: there were not significantly more adverse effects in the active treatment group compared to placebo (drowsiness, hypersomnia, sleepiness 10/152 versus 4/120; OR 1.64 (95 % CI 0.48 to 5.59; low certainty evidence). Analgesic-decongestant: seven trials (2575 participants). One trial reported on global effectiveness: 73% of participants in the analgesic-decongestant group reported a benefit compared with 52% in the control group (paracetamol) (OR of treatment failure 0.28, 95% CI 0.15 to 0.52; moderate certainty evidence; NNTB 4.7). Adverse effects: the decongestant-analgesic group experienced significantly more adverse effects than the control group (199/1122 versus 75/675; OR 1.62 95% CI 1.18 to 2.23; high certainty evidence; number needed to treat for an additional harmful outcome (NNTH 17). Antihistamine-analgesic-decongestant: six trials (1014 participants). Five trials reported on global effectiveness, of which two studies in adults could be pooled: global effect reported with active treatment (52%) and placebo (34%) was equivalent to a difference of less than one point on a four- or five-point scale; the OR of treatment failure was 0.47 (95% CI 0.33 to 0.67; low certainty evidence); NNTB 5.6 (95% CI 3.8 to 10.2). One trial in children aged 2 to 12 years, and two trials in adults found no beneficial effect. Adverse effects: in one trial 5/224 (2%) suffered adverse effects with the active treatment versus 9/208 (4%) with placebo. Two other trials reported no differences between treatment groups.
AUTHORS' CONCLUSIONS
We found a lack of data on the effectiveness of antihistamine-analgesic-decongestant combinations for the common cold. Based on these scarce data, the effect on individual symptoms is probably too small to be clinically relevant. The current evidence suggests that antihistamine-analgesic-decongestant combinations have some general benefit in adults and older children. These benefits must be weighed against the risk of adverse effects. There is no evidence of effectiveness in young children. In 2005, the US Food and Drug Administration issued a warning about adverse effects associated with the use of over-the-counter nasal preparations containing phenylpropanolamine.
Topics: Adolescent; Adult; Analgesics; Child; Child, Preschool; Common Cold; Cough; Histamine Antagonists; Humans; Nasal Decongestants; United States
PubMed: 35060618
DOI: 10.1002/14651858.CD004976.pub4 -
Audiology & Neuro-otology 2022Ménière's disease is characterized by recurrent episodes of vertigo, hearing loss, and tinnitus, often with a feeling of fullness in the ear. Although betahistine is...
BACKGROUND
Ménière's disease is characterized by recurrent episodes of vertigo, hearing loss, and tinnitus, often with a feeling of fullness in the ear. Although betahistine is thought to be specifically effective for Ménière's disease, no evidence for a benefit from the use of betahistine exists, despite its widespread use. Reassessment of the effect of betahistine for Ménière's disease is now warranted.
SEARCH METHODS
We searched for randomized controlled trials (RCTs) in the Central Register of Controlled Trials (CENTRAL), Ovid Medline, Ovid Embase, CINAHL, Web of Science, Clinicaltrials.gov, ICTRP, and additional sources for published and unpublished trials, in which betahistine was compared to placebo.
DATA COLLECTION AND ANALYSIS
Our outcomes involved vertigo, significant adverse effect (upper gastrointestinal discomfort), hearing loss, tinnitus, aural fullness, other adverse effects, and disease-specific health-related quality of life. We used GRADE to assess the quality of the evidence.
MAIN RESULTS
We included 10 studies: 5 studies used a crossover design and the remaining 5 were parallel-group RCTs. One study with a low risk of bias found no significant difference between the betahistine groups and placebo with respect to vertigo after a long-term follow-up period. No significant difference in the incidence of upper gastrointestinal discomfort was found in 2 studies (low-certainty evidence). No differences in hearing loss, tinnitus, or well-being and disease-specific health-related quality of life were found (low- to very low-certainty of evidence). Data on aural fullness could not be extracted. No significant difference between the betahistine and the placebo groups (low-certainty evidence) could be demonstrated in the other adverse effect outcome with respect to dull headache. The pooled risk ratio for other adverse effect in the long term demonstrated a lower risk in favor of placebo over betahistine.
CONCLUSIONS
High-quality studies evaluating the effect of betahistine on patients with Ménière's disease are lacking. However, one study with low risk of bias found no evidence of a difference in the effect of betahistine on the primary outcome, vertigo, in patients with Ménière's disease when compared to placebo. The main focus of future research should be on the use of comparable outcome measures by means of patient-reported outcome measures.
Topics: Betahistine; Deafness; Humans; Meniere Disease; Syndrome; Tinnitus; Vertigo
PubMed: 34233329
DOI: 10.1159/000515821 -
Journal of Personalized Medicine Aug 2021Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 2% of children in the United States. Biochemical abnormalities associated with ASD... (Review)
Review
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 2% of children in the United States. Biochemical abnormalities associated with ASD include impaired methylation and sulphation capacities along with low glutathione (GSH) redox capacity. Potential treatments for these abnormalities include cobalamin (B12). This systematic review collates the studies using B12 as a treatment in ASD. A total of 17 studies were identified; 4 were double-blind, placebo-controlled studies (2 examined B12 injections alone and 2 used B12 in an oral multivitamin); 1 was a prospective controlled study; 6 were prospective, uncontrolled studies, and 6 were retrospective (case series and reports). Most studies (83%) used oral or injected methylcobalamin (mB12), while the remaining studies did not specify the type of B12 used. Studies using subcutaneous mB12 injections (including 2 placebo-controlled studies) used a 64.5-75 µg/kg/dose. One study reported anemia in 2 ASD children with injected cyanocobalamin that resolved with switching to injected mB12. Two studies reported improvements in markers of mitochondrial metabolism. A meta-analysis of methylation metabolites demonstrated decreased S-adenosylhomocysteine (SAH), and increased methionine, S-adenosylmethionine (SAM), SAM/SAH ratio, and homocysteine (with small effect sizes) with mB12. Meta-analysis of the transsulfuration and redox metabolism metabolites demonstrated significant improvements with mB12 in oxidized glutathione (GSSG), cysteine, total glutathione (GSH), and total GSH/GSSG redox ratio with medium to large effect sizes. Improvements in methylation capacity and GSH redox ratio were significantly associated with clinical improvements (with a mean moderate effect size of 0.59) in core and associated ASD symptoms, including expressive communication, personal and domestic daily living skills, and interpersonal, play-leisure, and coping social skills, suggesting these biomarkers may predict response to B12. Other clinical improvements observed with B12 included sleep, gastrointestinal symptoms, hyperactivity, tantrums, nonverbal intellectual quotient, vision, eye contact, echolalia, stereotypy, anemia, and nocturnal enuresis. Adverse events identified by meta-analysis included hyperactivity (11.9%), irritability (3.4%), trouble sleeping (7.6%), aggression (1.8%), and worsening behaviors (7.7%) but were generally few, mild, not serious, and not significantly different compared to placebo. In one study, 78% of parents desired to continue mB12 injections after the study conclusion. Preliminary clinical evidence suggests that B12, particularly subcutaneously injected mB12, improves metabolic abnormalities in ASD along with clinical symptoms. Further large multicenter placebo-controlled studies are needed to confirm these data. B12 is a promising treatment for ASD.
PubMed: 34442428
DOI: 10.3390/jpm11080784 -
Nutrients Aug 2023To determine the effectiveness of whey protein (WP) supplementation during resistance exercise training (RET) vs. RET with or without placebo supplementation on skeletal... (Meta-Analysis)
Meta-Analysis Review
Effectiveness of Whey Protein Supplementation during Resistance Exercise Training on Skeletal Muscle Mass and Strength in Older People with Sarcopenia: A Systematic Review and Meta-Analysis.
OBJECTIVE
To determine the effectiveness of whey protein (WP) supplementation during resistance exercise training (RET) vs. RET with or without placebo supplementation on skeletal muscle mass, strength, and physical performance in older people with Sarcopenia.
METHODS
Electronic searches in the PubMed, Embase, Scopus, Web of Science, LILACS, SPORTDiscus, Epistemonikos, and CINAHL databases were performed until 20 January 2023. Randomized clinical trials conducted on sarcopenic adults aged 60 or older were included. The studies had to compare the effectiveness of the addition of supplements based on concentrated, isolated, or hydrolyzed whey protein during RET and compare it with RET with or without placebo supplementation on skeletal muscle mass and strength changes. The study selection process, data extraction, and risk of bias assessment were carried out by two independent reviewers.
RESULTS
Seven randomized clinical trials (591 participants) were included, and five of them provided data for quantitative synthesis. The overall pooled standardized mean difference (SMD) estimate showed a small effect size in favor of RET plus WP for skeletal muscle mass according to appendicular muscle index, with statistically significant differences compared with RET with or without the placebo group (SMD = 0.24; 95% CI, 0.05 to 0.42; = 0.01; = 0%, = 0.42). The overall pooled mean difference (MD) estimate showed a significant difference of +2.31 kg (MD = 2.31 kg; 95% CI, 0.01 to 4.6; = 0.05; = 81%, < 0.001) in handgrip strength in the RET plus WP group compared with the RET group with or without placebo. The narrative synthesis revealed discordance between the results of the studies on physical performance.
CONCLUSIONS
WP supplementation during RET is more effective in increasing handgrip strength and skeletal muscle mass in older people with Sarcopenia compared with RET with or without placebo supplementation. However, the effect sizes were small, and the MD did not exceed the minimally important clinical difference. The quality of the evidence was low to very low according, to the GRADE approach. Further research is needed in this field.
Topics: Adult; Humans; Aged; Sarcopenia; Whey Proteins; Muscle Strength; Muscle, Skeletal; Hand Strength; Resistance Training; Dietary Supplements
PubMed: 37571361
DOI: 10.3390/nu15153424 -
The Cochrane Database of Systematic... Sep 2022Oral nirmatrelvir/ritonavir (Paxlovid®) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death.... (Review)
Review
BACKGROUND
Oral nirmatrelvir/ritonavir (Paxlovid®) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. Due to its novelty, there are currently few published study results. It remains to be evaluated for which indications and patient populations the drug is suitable. OBJECTIVES: To assess the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid®) plus standard of care compared to standard of care with or without placebo, or any other intervention for treating COVID-19 and for preventing SARS-CoV-2 infection. To explore equity aspects in subgroup analyses. To keep up to date with the evolving evidence base using a living systematic review (LSR) approach and make new relevant studies available to readers in-between publication of review updates.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, Scopus, and WHO COVID-19 Global literature on coronavirus disease database, identifying completed and ongoing studies without language restrictions and incorporating studies up to 11 July 2022. This is a LSR. We conduct monthly update searches that are being made publicly available on the open science framework (OSF) platform.
SELECTION CRITERIA
Studies were eligible if they were randomized controlled trials (RCTs) comparing nirmatrelvir/ritonavir plus standard of care with standard of care with or without placebo, or any other intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS-CoV-2 infection. We screened all studies for research integrity. Studies were ineligible if they had been retracted, or if they were not prospectively registered including appropriate ethics approval.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology and used the Cochrane risk of bias 2 tool. We rated the certainty of evidence using the GRADE approach for the following outcomes: 1. to treat outpatients with mild COVID-19; 2. to treat inpatients with moderate-to-severe COVID-19: mortality, clinical worsening or improvement, quality of life, (serious) adverse events, and viral clearance; 3. to prevent SARS-CoV-2 infection in post-exposure prophylaxis (PEP); and 4. pre-exposure prophylaxis (PrEP) scenarios: SARS-CoV-2 infection, development of COVID-19 symptoms, mortality, admission to hospital, quality of life, and (serious) adverse events. We explored inequity by subgroup analysis for elderly people, socially-disadvantaged people with comorbidities, populations from LICs and LMICs, and people from different ethnic and racial backgrounds.
MAIN RESULTS
As of 11 July 2022, we included one RCT with 2246 participants in outpatient settings with mild symptomatic COVID-19 comparing nirmatrelvir/ritonavir plus standard of care with standard of care plus placebo. Trial participants were unvaccinated, without previous confirmed SARS-CoV-2 infection, had a symptom onset of no more than five days before randomization, and were at high risk for progression to severe disease. Prohibited prior or concomitant therapies included medications highly dependent on CYP3A4 for clearance and CYP3A4 inducers. We identified eight ongoing studies. Nirmatrelvir/ritonavir for treating COVID-19 in outpatient settings with asymptomatic or mild disease For the specific population of unvaccinated, high-risk patients nirmatrelvir/ritonavir plus standard of care compared to standard of care plus placebo may reduce all-cause mortality at 28 days (risk ratio (RR) 0.04, 95% confidence interval (CI) 0.00 to 0.68; 1 study, 2224 participants; estimated absolute effect: 11 deaths per 1000 people receiving placebo compared to 0 deaths per 1000 people receiving nirmatrelvir/ritonavir; low-certainty evidence, and admission to hospital or death within 28 days (RR 0.13, 95% CI 0.07 to 0.27; 1 study, 2224 participants; estimated absolute effect: 61 admissions or deaths per 1000 people receiving placebo compared to eight admissions or deaths per 1000 people receiving nirmatrelvir/ritonavir; low-certainty evidence). Nirmatrelvir/ritonavir plus standard of care may reduce serious adverse events during the study period compared to standard of care plus placebo (RR 0.24, 95% CI 0.15 to 0.41; 1 study, 2224 participants; low-certainty evidence). Nirmatrelvir/ritonavir plus standard of care probably has little or no effect on treatment-emergent adverse events (RR 0.95, 95% CI 0.82 to 1.10; 1 study, 2224 participants; moderate-certainty evidence), and probably increases treatment-related adverse events such as dysgeusia and diarrhoea during the study period compared to standard of care plus placebo (RR 2.06, 95% CI 1.44 to 2.95; 1 study, 2224 participants; moderate-certainty evidence). Nirmatrelvir/ritonavir plus standard of care probably decreases discontinuation of study drug due to adverse events compared to standard of care plus placebo (RR 0.49, 95% CI 0.30 to 0.80; 1 study, 2224 participants; moderate-certainty evidence). No study results were identified for improvement of clinical status, quality of life, and viral clearance. Subgroup analyses for equity Most study participants were younger than 65 years (87.1% of the : modified intention to treat (mITT1) population with 2085 participants), of white ethnicity (71.5%), and were from UMICs or HICs (92.1% of study centres). Data on comorbidities were insufficient. The outcome 'admission to hospital or death' was investigated for equity: age (< 65 years versus ≥ 65 years) and ethnicity (Asian versus Black versus White versus others). There was no difference between subgroups of age. The effects favoured treatment with nirmatrelvir/ritonavir for the White ethnic group. Estimated effects in the other ethnic groups included the line of no effect (RR = 1). No subgroups were reported for comorbidity status and World Bank country classification by income level. No subgroups were reported for other outcomes. Nirmatrelvir/ritonavir for treating COVID-19 in inpatient settings with moderate to severe disease No studies available. Nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection (PrEP and PEP) No studies available.
AUTHORS' CONCLUSIONS
There is low-certainty evidence that nirmatrelvir/ritonavir reduces the risk of all-cause mortality and hospital admission or death based on one trial investigating unvaccinated COVID-19 participants without previous infection that were at high risk and with symptom onset of no more than five days. There is low- to moderate-certainty evidence that nirmatrelvir/ritonavir is safe in people without prior or concomitant therapies including medications highly dependent on CYP3A4. Regarding equity aspects, except for ethnicity, no differences in effect size and direction were identified. No evidence is available on nirmatrelvir/ritonavir to treat hospitalized people with COVID-19 and to prevent a SARS-CoV-2 infection. We will continually update our search and make search results available on OSF.
Topics: Aged; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Humans; Ritonavir; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 36126225
DOI: 10.1002/14651858.CD015395.pub2