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PloS One 2016We performed a systematic review and meta-analysis of all the available evidence comparing efficacy and safety of oral prolonged released beclomethasone dipropionate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
We performed a systematic review and meta-analysis of all the available evidence comparing efficacy and safety of oral prolonged released beclomethasone dipropionate (BDP) to active oral controls in patients with mild-to-moderate ulcerative colitis (UC). A subgroup-analysis compared the effectiveness of BDP and 5-ASA.
METHODS
Literature research was performed in different databases, as well as manual search to identify abstracts from international meetings with data not included in extensive publications. Experts in the field and companies involved in BDP development and manufacture were contacted to identify unpublished studies used for registration purposes. Dichotomous data were pooled to obtain odds ratio meta-analysis.
RESULTS
Five randomized controlled trials that compared oral BDP 5mg/day vs. all oral active controls in treating UC were identified as eligible. Efficacy and safety have been addressed after 4-week treatment period. One study evaluated efficacy and safety of BDP vs. prednisone and 4 of BDP vs. 5-ASA. Treatment with oral BDP 5 mg/day induces a significant better clinical response compared to oral 5-ASA (OR 1.86, 95% CI = 1.23-2.82, P = 0.003). The effect is detectable even when the comparison to prednisone is added (OR 1.41, 95% CI = 1.03-1.93, P = 0.03). Data on remission indicate that the potential clinical efficacy of BDP may be better than 5-ASA (OR 1.55, 95% CI = 1.00-2.40, P = 0.05). This difference is lost when the comparison with prednisone is added (OR 1.30, 95% CI = 0.76-2.23, P = 0.34). The safety analysis showed no differences between BDP and 5-ASA (OR 0.55, 95% CI = 0.24-1.27, P = 0.16). The lack of difference is maintained even when the study with prednisone is added (OR 0.67, 95% CI = 0.44-1.01, P = 0.06). However, the trend of difference is clear and indicates a more favourable safety profile of BDP compared to 5-ASA and PD.
CONCLUSIONS
Oral prolonged release BDP showed a superior efficacy vs. oral 5-ASA in inducing clinical improvement of mild-to-moderate UC with a similar safety profile.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Beclomethasone; Colitis, Ulcerative; Drug Administration Schedule; Humans; Mesalamine; Patient Safety; Prednisone; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27846307
DOI: 10.1371/journal.pone.0166455 -
The Cochrane Database of Systematic... Apr 2017Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration.... (Review)
Review
BACKGROUND
Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration. Vaso-occlusive crises are common painful events responsible for a variety of clinical complications; overall mortality is increased and life expectancy decreased compared to the general population. Experimental studies suggest that intravenous magnesium has proven to be well-tolerated in individuals hospitalised for the immediate relief of acute (sudden onset) painful crisis and has the potential to decrease the length of hospital stay. Some in vitro studies and open studies of long-term oral magnesium showed promising effect on pain relief but failed to show its efficacy. The studies show that oral magnesium therapy may prevent sickle red blood cell dehydration and prevent recurrent painful episodes. There is a need to access evidence for the impact of oral and intravenous magnesium effect on frequency of pain, length of hospital stay and quality of life.
OBJECTIVES
To evaluate the effects of short-term intravenous magnesium on the length of hospital stay and quality of life in children and adults with sickle cell disease. To determine the effects of long-term oral magnesium therapy on the frequency of painful crises and the quality of life in children and adults with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 01 December 2016.Date of last search of other resources (clinical trials registries): 29 March 2017.
SELECTION CRITERIA
We searched for published and unpublished randomized controlled studies of oral or intravenous magnesium compared to placebo or no magnesium.
DATA COLLECTION AND ANALYSIS
Authors independently assessed the study quality and extracted the data using standard Cochrane methodologies.
MAIN RESULTS
We included five randomized placebo-controlled studies with a total of 386 participants (aged three to 53 years). Two shorter parallel studies (n = 306) compared intravenous magnesium sulphate to placebo (normal saline) for admission to hospital due to a vaso-occlusive crisis, for which we were able to analyse data. The quality of evidence was moderate for studies presenting this comparison mainly due to limitations due to risk of bias and imprecision. Two of the three longer-term studies comparing oral magnesium pidolate to placebo had a cross-over design. The third was a parallel factorial study which compared hydroxyurea and oral magnesium to each other and to placebo over a longer period of time; we only present the comparison of oral magnesium to placebo from this study. The quality of evidence was very low with uncertainty of the estimation.The eight-hourly dose levels in the two studies of intravenous magnesium were different; one used 100 mg/kg while the second used 40 mg/kg. Only one of these studies (n = 104) reported the mean daily pain score while hospitalised (a non-significant difference between groups, moderate quality evidence). The second study (n = 202) reported a number of child- and parent-reported quality of life scores. None of the scores showed any difference between treatment groups (low quality evidence). Data from one study (n = 106) showed no difference in length of stay in hospital between groups (low quality evidence). Both studies reported on adverse events, but not defined by severity as we had planned. One study showed significantly more participants receiving intravenous magnesium experienced warmth at infusion site compared to placebo; there were no differences between groups for other adverse events (low quality evidence).Three studies (n = 80) compared oral magnesium pidolate to placebo. None of them reported data which we were able to analyse. One study (n = 24) reported on the number of painful days and stated there was no difference between two groups (low quality evidence). None of the studies reported on quality of life or length of hospital stay. Two studies (n = 68) reported there were no differences in levels of magnesium in either plasma or red blood cells (moderate quality evidence). Two studies (n = 56) reported adverse events. One reported episodes of mild diarrhoea and headache, all of which resolved without stopping treatment. The second study reported adverse events as gastrointestinal disorders, headache or migraine, upper respiratory infections and rash; which were all evenly distributed across treatment groups (moderate quality evidence).
AUTHORS' CONCLUSIONS
Moderate to low quality evidence showed neither intravenous magnesium and oral magnesium therapy has an effect on reducing painful crisis, length of hospital stay and changing quality of life in treating sickle cell disease. Therefore, no definitive conclusions can be made regarding its clinical benefit. Further randomized controlled studies, perhaps multicentre, are necessary to establish whether intravenous and oral magnesium therapies have any effect on improving the health of people with sickle cell disease.
Topics: Administration, Oral; Adolescent; Adult; Anemia, Sickle Cell; Antisickling Agents; Child; Child, Preschool; Humans; Hydroxyurea; Injections, Intravenous; Magnesium; Magnesium Sulfate; Middle Aged; Pain Measurement; Parents; Pyrrolidonecarboxylic Acid; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 28409830
DOI: 10.1002/14651858.CD011358.pub2 -
The Lancet. Gastroenterology &... Feb 2017Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin.
METHODS
For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs).
FINDINGS
We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47-1·08]; warfarin vs dabigatran 0·88 [0·59-1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42-2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20-1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07-0.76]) or dabigatran (0.24 [0.07-0.77]).
INTERPRETATION
Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with warfarin or low-molecular-weight heparin. These findings support the continued use of direct oral anticoagulants.
FUNDING
Leeds Teaching Hospitals Charitable Foundation.
Topics: Administration, Oral; Anticoagulants; Dabigatran; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Network Meta-Analysis; Risk Factors; Warfarin
PubMed: 28403994
DOI: 10.1016/S2468-1253(16)30162-5 -
Annals of Palliative Medicine Dec 2021With the continuous improvement of human living standards, more and more dental patients are requiring oral implant restoration treatment. However, there is still... (Meta-Analysis)
Meta-Analysis
BACKGROUND
With the continuous improvement of human living standards, more and more dental patients are requiring oral implant restoration treatment. However, there is still controversy regarding the influence of risk factors such as osteoporosis, radiotherapy, diabetes, and smoking on the failure of oral implants. This study aimed to explore the correlation between risk factors and failure of oral implant restoration treatment.
METHODS
The databases of China National Knowledge Infrastructure (CNKI), Baidu Academic, Weipu, Wanfang, PubMed, EBSCO, Medline, Web of knowledge, Ovid, and the Cochrane Library were searched. The search strategies included: subject terms related to research results such as survival, osseointegration, failure, removal, replacement, and loss; related to risk factors: osteoporosis, head and neck cancer, diabetes, and smoking; and oral implantology as a keyword.
RESULTS
Thirty-two articles were included in meta-analysis, there was a high heterogeneity between radiotherapy and dental implant failure (I2=71.6%, P=0.000), and there was an obvious correlation between radiotherapy and dental implant failure [relative risk (RR) =2.09, 95% confidential interval (CI): 1.68-2.61]. There was heterogeneity between diabetes and oral implant failure in the included articles (I2=59.6%, P=0.084). There was no remarkable correlation between osteoporosis and dental implant failure (RR =1.19, 95% CI: 0.81-1.74). There was a high heterogeneity between smoking and dental implant failure in the included articles (I2=33.8%, P=0.092), showing obvious correlation (RR =1.80, 95% CI: 1.53-2.11).
DISCUSSION
The results of meta-analysis confirmed that radiotherapy and smoking were greatly associated with oral implant failure.
Topics: Administration, Oral; Diabetes Mellitus; Humans; Osteoporosis; Risk Factors; Smoking
PubMed: 35016469
DOI: 10.21037/apm-21-3449 -
The Lancet. Infectious Diseases Feb 2019Oral vaccines underperform in low-income and middle-income countries compared with in high-income countries. Whether interventions can improve oral vaccine performance... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral vaccines underperform in low-income and middle-income countries compared with in high-income countries. Whether interventions can improve oral vaccine performance is uncertain.
METHODS
We did a systematic review and meta-analysis of interventions designed to increase oral vaccine efficacy or immunogenicity. We searched Ovid-MEDLINE and Embase for trials published until Oct 23, 2017. Inclusion criteria for meta-analysis were two or more studies per intervention category and available seroconversion data. We did random-effects meta-analyses to produce summary relative risk (RR) estimates. This study is registered with PROSPERO (CRD42017060608).
FINDINGS
Of 2843 studies identified, 87 were eligible for qualitative synthesis and 66 for meta-analysis. 22 different interventions were assessed for oral poliovirus vaccine (OPV), oral rotavirus vaccine (RVV), oral cholera vaccine (OCV), and oral typhoid vaccines. There was generally high heterogeneity. Seroconversion to RVV was significantly increased by delaying the first RVV dose by 4 weeks (RR 1·37, 95% CI 1·16-1·62) and OPV seroconversion was increased with monovalent or bivalent OPV compared with trivalent OPV (RR 1·51, 95% CI 1·20-1·91). There was some evidence that separating RVV and OPV increased RVV seroconversion (RR 1·21, 95% CI 1·00-1·47) and that higher vaccine inoculum improved OCV seroconversion (RR 1·12, 95% CI 1·00-1·26). There was no evidence of effect for anthelmintics, antibiotics, probiotics, zinc, vitamin A, withholding breastfeeding, extra doses, or vaccine buffering.
INTERPRETATION
Most strategies did not improve oral vaccine performance. Delaying RVV and reducing OPV valence should be considered within immunisation programmes to reduce global enteric disease. New strategies to address the gap in oral vaccine efficacy are urgently required.
FUNDING
Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and WHO Polio Research Committee.
Topics: Administration, Oral; Adolescent; Adult; Child; Child, Preschool; Cholera; Cholera Vaccines; Female; Humans; Immunogenicity, Vaccine; Infant; Infant, Newborn; Male; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Salmonella typhi; Seroconversion; Treatment Outcome; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccination; Vibrio cholerae; Young Adult
PubMed: 30712836
DOI: 10.1016/S1473-3099(18)30602-9 -
The Cochrane Database of Systematic... Sep 2014Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or empirically to patients with persistent fever.
OBJECTIVES
To compare the effect of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia.
SEARCH METHODS
We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.
SELECTION CRITERIA
Randomised clinical trials comparing fluconazole with amphotericin B.
DATA COLLECTION AND ANALYSIS
The two review authors independently assessed trial eligibility and risk of bias, and abstracted data.
MAIN RESULTS
Seventeen trials (3798 patients, 381 deaths) were included. In two large three-armed trials, results for amphotericin B were combined with results for nystatin in a 'polyene' group. Because nystatin is an ineffective drug in these circumstances, this approach creates a bias in favour of fluconazole. Furthermore, most patients were randomised to oral amphotericin B, which is poorly absorbed and poorly documented. There was overlap among the 'polyene' trials but we were unable to obtain any information from the trial authors or from Pfizer, the manufacturer of fluconazole, to clarify these issues. There were no significant differences in effect between fluconazole and amphotericin B, but the confidence intervals were wide. More patients dropped out of the study when they received amphotericin B, but as none of the trials were blinded decisions on premature interruption of therapy could have been biased. Furthermore, amphotericin B was not given under optimal circumstances, with premedication to reduce infusion-related toxicity, slow infusion, and with fluid, potassium and magnesium supplements to prevent nephrotoxicity. The major harms were hepatic impairment and gastrointestinal adverse effects with fluconazole and infusion-related toxicity, renal impairment and gastrointestinal adverse effects with amphotericin B. For the 2011 and 2014 updates no additional trials were identified for inclusion.
AUTHORS' CONCLUSIONS
Amphotericin B has been disfavoured in several of the trials through their design or analysis, or both. Since intravenous amphotericin B is the only antifungal agent for which an effect on mortality has been shown, and since it is considerably cheaper than fluconazole, it should be the preferred agent.
Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Confidence Intervals; Fluconazole; Humans; Injections, Intravenous; Mycoses; Neoplasms; Neutropenia; Nystatin; Odds Ratio; Randomized Controlled Trials as Topic
PubMed: 25188769
DOI: 10.1002/14651858.CD000239.pub2 -
The Cochrane Database of Systematic... Nov 2016Tinnitus is the perception of sound without external acoustic stimuli. Patients with severe tinnitus may have physical and psychological complaints and their tinnitus... (Review)
Review
BACKGROUND
Tinnitus is the perception of sound without external acoustic stimuli. Patients with severe tinnitus may have physical and psychological complaints and their tinnitus can cause deterioration in their quality of life. At present no specific therapy for tinnitus has been found to be satisfactory in all patients. In recent decades, a number of reports have suggested that oral zinc supplementation may be effective in the management of tinnitus. Since zinc has a role in cochlear physiology and in the synapses of the auditory system, there is a plausible mechanism of action for this treatment.
OBJECTIVES
To evaluate the effectiveness and safety of oral zinc supplementation in the management of patients with tinnitus.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2016, Issue 6); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 July 2016.
SELECTION CRITERIA
Randomised controlled trials comparing zinc supplementation versus placebo in adults (18 years and over) with tinnitus.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures recommended by Cochrane. Our primary outcome measures were improvement in tinnitus severity and disability, measured by a validated tinnitus-specific questionnaire, and adverse effects. Secondary outcomes were quality of life, change in socioeconomic impact associated with work, change in anxiety and depression disorders, change in psychoacoustic parameters, change in tinnitus loudness, change in overall severity of tinnitus and change in thresholds on pure tone audiometry. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
MAIN RESULTS
We included three trials involving a total of 209 participants. The studies were at moderate to high risk of bias. All included studies had differences in participant selection criteria, length of follow-up and outcome measurement, precluding a meta-analysis. The participants were all adults over 18 years with subjective tinnitus, but one study conducted in 2013 (n = 109) included only elderly patients. Improvement in tinnitus severity and disabilityOnly the study in elderly patients used a validated instrument (Tinnitus Handicap Questionnaire) for this primary outcome. The authors of this cross-over study did not report the results of the two phases separately and found no significant differences in the proportion of patients reporting tinnitus improvement at four months of follow-up: 5% (5/93) versus 2% (2/94) in the zinc and placebo groups, respectively (risk ratio (RR) 2.53, 95% confidence interval (CI) 0.50 to 12.70; very low-quality evidence).None of the included studies reported any significant adverse effects. Secondary outcomesFor the secondary outcome change in tinnitus loudness, one study reported no significant difference between the zinc and placebo groups after eight weeks: mean difference in tinnitus loudness -9.71 dB (95% CI -25.53 to 6.11; very low-quality evidence). Another study also measured tinnitus loudness but used a 0- to 100-point scale. The authors of this second study reported no significant difference between the zinc and placebo groups after four months: mean difference in tinnitus loudness rating scores 0.50 (95% CI -5.08 to 6.08; very low-quality evidence).Two studies used unvalidated instruments to assess tinnitus severity. One (with 50 participants) reported the severity of tinnitus using a non-validated scale (0 to 7 points) and found no significant difference in subjective tinnitus scores between the zinc and placebo groups at the end of eight weeks of follow-up (mean difference (MD) -1.41, 95% CI -2.97 to 0.15; very low-quality evidence). A third trial (n = 50) also evaluated the improvement of tinnitus using a non-validated instrument (a 0 to 10 scale: 10 = severe and unbearable tinnitus). In this study, after eight weeks there was no difference in the proportion of patients with improvement in their tinnitus, 8.7% (2/23) treated with zinc versus 8% (2/25) of those who received a placebo (RR 1.09, 95% CI 0.17 to 7.10, very low-quality evidence).None of the included studies reported any of our other secondary outcomes (quality of life, change in socioeconomic impact associated with work, change in anxiety and depression disorders, change in psychoacoustic parameters or change in thresholds on pure tone audiometry).
AUTHORS' CONCLUSIONS
We found no evidence that the use of oral zinc supplementation improves symptoms in adults with tinnitus.
Topics: Administration, Oral; Adult; Aged; Humans; Middle Aged; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Tinnitus; Treatment Outcome; Zinc
PubMed: 27879981
DOI: 10.1002/14651858.CD009832.pub2 -
The Cochrane Database of Systematic... Jan 2017Miscarriage occurs in 10% to 15% of pregnancies. The traditional treatment, after miscarriage, has been to perform surgery to remove any remaining placental tissues in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Miscarriage occurs in 10% to 15% of pregnancies. The traditional treatment, after miscarriage, has been to perform surgery to remove any remaining placental tissues in the uterus ('evacuation of uterus'). However, medical treatments, or expectant care (no treatment), may also be effective, safe, and acceptable.
OBJECTIVES
To assess the effectiveness, safety, and acceptability of any medical treatment for incomplete miscarriage (before 24 weeks).
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (13 May 2016) and reference lists of retrieved papers.
SELECTION CRITERIA
We included randomised controlled trials comparing medical treatment with expectant care or surgery, or alternative methods of medical treatment. We excluded quasi-randomised trials.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the studies for inclusion, assessed risk of bias, and carried out data extraction. Data entry was checked. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
We included 24 studies (5577 women). There were no trials specifically of miscarriage treatment after 13 weeks' gestation.Three trials involving 335 women compared misoprostol treatment (all vaginally administered) with expectant care. There was no difference in complete miscarriage (average risk ratio (RR) 1.23, 95% confidence interval (CI) 0.72 to 2.10; 2 studies, 150 women, random-effects; very low-quality evidence), or in the need for surgical evacuation (average RR 0.62, 95% CI 0.17 to 2.26; 2 studies, 308 women, random-effects; low-quality evidence). There were few data on 'deaths or serious complications'. For unplanned surgical intervention, we did not identify any difference between misoprostol and expectant care (average RR 0.62, 95% CI 0.17 to 2.26; 2 studies, 308 women, random-effects; low-quality evidence).Sixteen trials involving 4044 women addressed the comparison of misoprostol (7 studies used oral administration, 6 studies used vaginal, 2 studies sublingual, 1 study combined vaginal + oral) with surgical evacuation. There was a slightly lower incidence of complete miscarriage with misoprostol (average RR 0.96, 95% CI 0.94 to 0.98; 15 studies, 3862 women, random-effects; very low-quality evidence) but with success rate high for both methods. Overall, there were fewer surgical evacuations with misoprostol (average RR 0.05, 95% CI 0.02 to 0.11; 13 studies, 3070 women, random-effects; very low-quality evidence) but more unplanned procedures (average RR 5.03, 95% CI 2.71 to 9.35; 11 studies, 2690 women, random-effects; low-quality evidence). There were few data on 'deaths or serious complications'. Nausea was more common with misoprostol (average RR 2.50, 95% CI 1.53 to 4.09; 11 studies, 3015 women, random-effects; low-quality evidence). We did not identify any difference in women's satisfaction between misoprostol and surgery (average RR 1.00, 95% CI 0.99 to 1.00; 9 studies, 3349 women, random-effects; moderate-quality evidence). More women had vomiting and diarrhoea with misoprostol compared with surgery (vomiting: average RR 1.97, 95% CI 1.36 to 2.85; 10 studies, 2977 women, random-effects; moderate-quality evidence; diarrhoea: average RR 4.82, 95% CI 1.09 to 21.32; 4 studies, 757 women, random-effects; moderate-quality evidence).Five trials compared different routes of administration, or doses, or both, of misoprostol. There was no clear evidence of one regimen being superior to another. Limited evidence suggests that women generally seem satisfied with their care. Long-term follow-up from one included study identified no difference in subsequent fertility between the three approaches.
AUTHORS' CONCLUSIONS
The available evidence suggests that medical treatment, with misoprostol, and expectant care are both acceptable alternatives to routine surgical evacuation given the availability of health service resources to support all three approaches. Further studies, including long-term follow-up, are clearly needed to confirm these findings. There is an urgent need for studies on women who miscarry at more than 13 weeks' gestation.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Incomplete; Administration, Intravaginal; Administration, Oral; Diarrhea; Extraction, Obstetrical; Female; Gestational Age; Humans; Misoprostol; Nausea; Pregnancy; Pregnancy Trimester, First; Randomized Controlled Trials as Topic; Vomiting; Watchful Waiting
PubMed: 28138973
DOI: 10.1002/14651858.CD007223.pub4 -
CNS Drugs Aug 2023Considering the improvement in adherence and convenience, once-monthly paliperidone palmitate (PP1M) has been increasingly used in the treatment of schizophrenia.... (Meta-Analysis)
Meta-Analysis
Effectiveness and Safety of Switching from Oral Antipsychotics to Once-Monthly Paliperidone Palmitate (PP1M) in the Management of Schizophrenia: A Systematic Review and Meta-Analysis.
BACKGROUND
Considering the improvement in adherence and convenience, once-monthly paliperidone palmitate (PP1M) has been increasingly used in the treatment of schizophrenia. However, the outcomes for patients who switch from oral antipsychotics (OAPs) to PP1M have not been reliably assessed. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of PP1M in the management of patients with schizophrenia with a prior history of OAP use.
METHODS
We conducted a systematic search in PubMed, EMBASE, and the Cochrane Library on 19 July 2022 to identify eligible studies. All studies that examined the effectiveness and safety of switching from OAPs to PP1M in patients with schizophrenia were included. The primary outcomes were relapse rate, hospitalisation rate, and the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score. The secondary outcomes included the changed number of inpatient visits, changed length of stay hospitalisation, change from baseline in the Clinical Global Impressions-Severity (CGI-S) score and the personal and social performance (PSP) total score, response rate, proportion of treatment discontinuation, and adverse events. We included randomised-controlled trials (RCTs), single-arm studies, and observational studies. Case reports, case series, and reviews were excluded. The quality assessment of included studies was performed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB2), the 9-point Newcastle-Ottawa Scale (NOS) instrument for non-randomised studies and cohort studies, and the 12-item National Institutes of Health (NIH) quality assessment tool for before-after (Pre-Post) study without control group. Follow-up times were reported as short- (≤ 13 weeks), medium- (14-26 weeks), and long term (≥ 27 weeks). Data were pooled using meta-analysis.
RESULTS
Fifteen studies with a total of 4740 patients were included. The long-term relapse rates and hospitalisation rates were 12% (95% CI 0.07-0.18) and 18% (95% CI 0.15-0.20), respectively. The short-, medium-, and long-term change in PANSS total score was - 21.69 (95% CI - 30.02 to -13.36), - 14.98 (95% CI - 21.45 to - 8.51) and - 17.88 (95% CI - 31.94 to -3.82), respectively. Approximately 50% of patients reported at least a 30% reduction in the PANSS score at the short-term follow-up. Improvements in CGI-S and PSP score were observed during various periods. There was a reduction in the length of stay hospitalisation and the number of inpatient visits at the medium- and long-term follow-ups. Low discontinuation and adverse event rates were reported.
CONCLUSION
Based on our findings, this study may support the efficacy and safety of switching from OAPs to PP1M for the treatment of patients with schizophrenia. Future large-scale studies are warranted to confirm our findings.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Schizophrenia; Administration, Oral; Recurrence; Chronic Disease
PubMed: 37490267
DOI: 10.1007/s40263-023-01028-1 -
The Lancet. Global Health Jan 2020About 3·7 billion doses of ivermectin have been distributed in mass drug administration (MDA) campaigns globally over the past 30 years. At 10-100 times higher than... (Meta-Analysis)
Meta-Analysis
BACKGROUND
About 3·7 billion doses of ivermectin have been distributed in mass drug administration (MDA) campaigns globally over the past 30 years. At 10-100 times higher than current human doses, ivermectin is a known teratogen in mammals. During these campaigns with recommended doses, pregnant women might be inadvertently exposed. We therefore aimed to evaluate the existing evidence for serious and non-serious adverse events after ivermectin exposure in pregnant women.
METHODS
For this systematic review and meta-analysis, we searched relevant databases and trial registry platforms on July 15, 2018, for randomised controlled trials (RCTs) and observational studies that reported adverse events in pregnant women. We did not use language or date restrictions. Outcomes of interest were spontaneous abortions, stillbirths, congenital anomalies, and neonatal death (serious adverse events), as well as maternal morbidity, preterm births, and low birthweight (adverse events). The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias Tool for RCTs. We did the meta-analysis of observational studies and RCTs separately. The quality of evidence was assessed using the GRADE approach. The study protocol is registered with PROSPERO, protocol CRD42016046914.
FINDINGS
We identified 147 records, of which only five observational studies and one RCT were included for quantitative analysis; these studies were published between 1990 and 2008, and were done in six African countries. 893 women with 899 pregancy outcomes were included, of whom 496 pregnant women (500 pregnancy outcomes) received ivermectin inadvertently during MDA campaigns in the observational studies and 397 pregnant women (399 pregnancy outcomes) purposely received ivermectin as part of the open-label RCT. No study reported neonatal deaths, maternal morbidity, preterm births, or low birthweight. It is unclear whether exposure to ivermectin during pregnancy increases the risk of spontaneous abortions and stillbirths (odds ratio [OR] 1·15 [95% CI 0·75-1·78] with very low certainty of evidence for the four observational studies and 0·62 [0·18-2·14] with very low certainty of evidence for the RCT) or congenital anomalies (OR 1·69 [95% CI 0·83-3·41] with very low certainty of evidence for the five observational studies and 1·10 [0·07-17·65] with very low certainty of evidence for the RCT).
INTERPRETATION
There is insufficient evidence to conclude on the safety profile of ivermectin during pregnancy. Treatment campaigns should focus additional efforts on preventing inadvertent treatment of pregnant women.
FUNDING
Unitaid.
Topics: Administration, Oral; Adult; Female; Humans; Ivermectin; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Teratogens
PubMed: 31839144
DOI: 10.1016/S2214-109X(19)30453-X