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  1. Than NN, Soe HHK, Palaniappan SK, Abas AB, De Franceschi L
    Cochrane Database Syst Rev, 2019 09 09;9:CD011358.
    PMID: 31498421 DOI: 10.1002/14651858.CD011358.pub3
    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. This is an updated version of the review.

    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: 03 February 2019.Date of last search of other resources (clinical trials registries): 04 April 2019.

    SELECTION CRITERIA: We searched for published and unpublished randomized controlled studies of oral or intravenous magnesium compared to placebo or no magnesium.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). Of these, 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 in 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.

  2. Than NN, Soe HHK, Palaniappan SK, Abas AB, De Franceschi L
    Cochrane Database Syst Rev, 2017 Apr 14;4:CD011358.
    PMID: 28409830 DOI: 10.1002/14651858.CD011358.pub2
    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.

  3. Ni H, Aye SZ, Naing C
    Cochrane Database Syst Rev, 2022 May 26;5(5):CD013506.
    PMID: 35616126 DOI: 10.1002/14651858.CD013506.pub2
    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic and progressive disease, often punctuated by recurrent flare-ups or exacerbations. Magnesium sulfate, having a bronchodilatory effect, may have a potential role as an adjunct treatment in COPD exacerbations. However, comprehensive evidence of its effects is required to facilitate clinical decision-making.

    OBJECTIVES: To assess the effects of magnesium sulfate for acute exacerbations of chronic obstructive pulmonary disease in adults.

    SEARCH METHODS: We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) trials portal, EU Clinical Trials Register and Iranian Registry of Clinical Trials. We also searched the proceedings of major respiratory conferences and reference lists of included studies up to 2 August 2021.

    SELECTION CRITERIA: We included single- or double-blind parallel-group randomised controlled trials (RCTs) assessing magnesium sulfate in adults with COPD exacerbations. We excluded cross-over trials.

    DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias. The primary outcomes were: hospital admissions (from the emergency room); need for non-invasive ventilation (NIV), assisted ventilation or admission to intensive-care unit (ICU); and serious adverse events. Secondary outcomes were: length of hospital stay, mortality, adverse events, dyspnoea score, lung function and blood gas measurements. We assessed confidence in the evidence using GRADE methodology. For missing data, we contacted the study investigators.

    MAIN RESULTS: We identified 11 RCTs (10 double-blind and 1 single-blind) with a total 762 participants. The mean age of participants ranged from 62 to 76 years. Trials were single- or two-centre trials conducted in Iran, New Zealand, Nepal, Turkey, the UK, Tunisia and the USA between 2004 and 2018. We judged studies to be at low or unclear risk of bias for most of the domains. Three studies were at high risk for blinding and other biases.  Intravenous magnesium sulfate versus placebo Seven studies (24 to 77 participants) were included. Fewer people may require hospital admission with magnesium infusion compared to placebo (odds ratio (OR) 0.45, 95% CI 0.23 to 0.88; number needed to treat for an additional beneficial outcome (NNTB) = 7; 3 studies, 170 participants; low-certainty evidence). Intravenous magnesium may result in little to no difference in the requirement for non-invasive ventilation (OR 0.74, 95% CI 0.31 to 1.75; very low-certainty evidence). There were no reported cases of endotracheal intubation (2 studies, 107 participants) or serious adverse events (1 study, 77 participants) in either group. Included studies did not report intensive care unit (ICU) admission or deaths. Magnesium infusion may reduce the length of hospital stay by a mean difference (MD) of 2.7 days (95% CI 4.73 days to 0.66 days; 2 studies, 54 participants; low-certainty evidence) and improve dyspnoea score by a standardised mean difference of -1.40 (95% CI -1.83 to -0.96; 2 studies, 101 participants; low-certainty evidence). We were uncertain about the effect of magnesium infusion on improving lung function or oxygen saturation. For all adverse events, the Peto OR was 0.14 (95% CI 0.02 to 1.00; 102 participants); however, the event rate was too low to reach a robust conclusion.  Nebulised magnesium sulfate versus placebo Three studies (20 to 172 participants) were included. Magnesium inhalation may have little to no impact on hospital admission (OR 0.77, 95% CI 0.21 to 2.82; very low-certainty evidence) or need for ventilatory support (NIV or mechanical ventilation) (OR 0.33, 95% CI 0.01 to 8.20; very low-certainty evidence). It may result in fewer ICU admissions compared to placebo (OR 0.39, 95% CI 0.15 to 1.00; very low-certainty evidence) and improvement in dyspnoea (MD -14.37, 95% CI -26.00 to -2.74; 1 study, 20 participants; very low-certainty evidence). There were no serious adverse events reported in either group. There was one reported death in the placebo arm in one trial, but the number of participants was too small for a conclusion. There was limited evidence about the effect of magnesium inhalation on length of hospital stay, lung function outcomes or oxygen saturation. Included studies did not report adverse events.  Magnesium sulfate versus ipratropium bromide  A single study with 124 participants assessed nebulised magnesium sulfate plus intravenous magnesium infusion versus nebulised ipratropium plus intravenous normal saline. There was little to no difference between these groups in terms of hospital admission (OR 1.62, 95% CI 0.78 to 3.37), endotracheal intubation (OR 1.69, 95% CI 0.61 to 4.71) and length of hospital stay (MD 1.10 days, 95% CI -0.22 to 2.42), all with very low-certainty evidence. There were no data available for non-invasive ventilation, ICU admission and serious adverse events. Adverse events were not reported.  AUTHORS' CONCLUSIONS: Intravenous magnesium sulfate may be associated with fewer hospital admissions, reduced length of hospital stay and improved dyspnoea scores compared to placebo. There is no evidence of a difference between magnesium infusion and placebo for NIV, lung function, oxygen saturation or adverse events. We found no evidence for ICU admission, endotracheal intubation, serious adverse events or mortality. For nebulised magnesium sulfate, we are unable to draw conclusions about its effects in COPD exacerbations for most of the outcomes. Studies reported possibly lower ICU admissions and a lesser degree of dyspnoea with magnesium inhalation compared to placebo; however, larger studies are required to yield a more precise estimate for these outcomes. Similarly, we could not identify any robust evidence for magnesium sulfate compared to ipratropium bromide. Future well-designed multicentre trials with larger samples are required, including subgroups according to severity of exacerbations and COPD phenotypes.

  4. Ho JJ, Rasa G
    PMID: 17636807
    Persistent pulmonary hypertension of the newborn (PPHN) occurs in approximately 1.9 per 1000 newborns and may be more frequent in developing countries. There is strong evidence for the use of inhaled nitric oxide (iNO) and extra corporeal membrane oxygenation (ECMO) in the treatment of PPHN. However, many developing countries do not have access or the technical expertise required for these expensive therapies. Magnesium sulfate is a potent vasodilator and hence has the potential to reduce the high pulmonary arterial pressures associated with PPHN. If magnesium sulfate were found to be effective in the treatment of PPHN, this could be a cost effective and potentially life-saving therapy.
  5. Prashanti E, Sumanth KN, Renjith George P, Karanth L, Soe HH
    PMID: 26423025 DOI: 10.1002/14651858.CD011116.pub2
    Gag reflex is an involuntary defence mechanism to protect the pharynx and throat from foreign objects. Gagging is a common problem encountered during dental treatment, which makes therapeutic procedures distressing and often difficult or even impossible to perform. Various interventions can be used to control the gag reflex; for example, anti-nausea medicines, sedatives, local and general anaesthetics, herbal remedies, behavioural therapies, acupressure, acupuncture, and prosthetic devices.
  6. Eachempati P, Kumbargere Nagraj S, Kiran Kumar Krishanappa S, George RP, Soe HHK, Karanth L
    Cochrane Database Syst Rev, 2019 11 13;2019(11).
    PMID: 31721146 DOI: 10.1002/14651858.CD011116.pub3
    BACKGROUND: The gag reflex is an involuntary defence mechanism to protect the pharynx and throat from foreign objects. Gagging is a common problem encountered during dental treatment, making therapeutic procedures distressing and often difficult or even impossible to perform. Various interventions can be used to control the gag reflex: anti-nausea medicines, sedatives, local and general anaesthetics, herbal remedies, behavioural therapies, acupressure, acupuncture, laser, and prosthetic devices. This is an update of the Cochrane Review first published in 2015.

    OBJECTIVES: To assess the effects of pharmacological and non-pharmacological interventions for the management of gagging in people undergoing dental treatment.

    SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the Cochrane Oral Health's Trials Register (to 18 March 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 2) in the Cochrane Library (searched 18 March 2019), MEDLINE Ovid (1946 to 18 March 2019), Embase Ovid (1980 to 18 March 2019), CINAHL EBSCO (1937 to 18 March 2019), AMED Ovid (1985 to 18 March 2019), and the proceedings of the International Association for Dental Research (IADR) online (2001 to 18 March 2019). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. We also conducted forwards citation searching on the included studies via Google Scholar. No restrictions were placed on the language or date of publication when searching the electronic databases.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs), involving people who were given a pharmacological or non-pharmacological intervention to manage gagging that interfered with dental treatment. We excluded quasi-RCTs. We excluded trials with participants who had central or peripheral nervous system disorders, who had oral lesions or were on systemic medications that might affect the gag sensation, or had undergone surgery which might alter anatomy permanently.

    DATA COLLECTION AND ANALYSIS: We independently selected trials, extracted data, and assessed risk of bias. We followed Cochrane's statistical guidelines. We assessed the overall certainty of the evidence using GRADE.

    MAIN RESULTS: We included four trials at unclear risk of bias with 328 participants (263 adults and 65 children who were four years or older), in which one trial compared acupuncture and acupressure (with thumb, device and sea band) at P6 (point located three-finger breadths below the wrist on the inner forearm in between the two tendons) to sham acupuncture and acupressure with and without sedation. One trial compared acupuncture at P6 point to sham acupuncture. These trials reported both completion of dental procedure and reduction in gagging (assessor and patient reported) as their outcomes. One cross-over and one split-mouth trial studied the effect of laser at P6 point compared to control. One trial reported reduction in gagging and another reported presence or absence of gagging during dental procedure. Acupuncture at P6 showed uncertain evidence regarding the successful completion of dental procedure (RR 1.78, 95% CI 1.05 to 3.01; two trials, 59 participants; very low-certainty evidence) and uncertain evidence regarding the reduction in gagging (RR 2.57, 95% CI 1.12 to 5.89; one trial, 26 participants; very low-certainty evidence) in comparison to sham acupuncture. Acupuncture at P6 with sedation did not show any difference when compared to sham acupuncture with sedation (RR 1.08, 95% CI 0.91 to 1.28; one trial, 34 participants; very low-certainty evidence). Acupressure using thumb pressure with or without sedation showed no clear difference in completing dental procedure (RR 0.96, 95% CI 0.84 to 1.10; one trial, 39 participants; very low-certainty evidence; and RR 0.85, 95% CI 0.50 to 1.46; one trial, 30 participants; very low-certainty evidence; respectively), or reduction in gagging (RR 1.06, 95% CI 0.92 to 1.23; one trial, 39 participants; very low-certainty evidence; and RR 0.92, 95% CI 0.60 to 1.41; one trial, 30 participants; very low-certainty evidence; respectively) when compared to sham acupressure with or without sedation. Acupressure at P6 with device showed uncertain evidence regarding the successful completion of dental procedure (RR 2.63, 95% CI 1.33 to 5.18; one trial, 34 participants; very low-certainty evidence) and uncertain evidence regarding the reduction in gagging (RR 3.94, 95% CI 1.63 to 9.53; one trial, 34 participants; very low-certainty evidence) when compared to sham acupressure. However, device combined with sedation showed no difference for either outcome (RR 1.16, 95% CI 0.90 to 1.48; one trial, 27 participants; very low-certainty evidence; and RR 1.26, 95% CI 0.93 to 1.69; one trial, 27 participants; very low-certainty evidence; respectively). Acupressure using a sea band with or without sedation showed no clear difference in completing dental procedure (RR 0.88, 95% CI 0.67 to 1.17; one trial, 21 participants; very low-certainty evidence; and RR 1.80, 95% CI 0.63 to 5.16; one trial, 19 participants; very low-certainty evidence; respectively), or reduction in gagging (RR 0.88, 95% CI 0.67 to 1.17; one trial, 21 participants; very low-certainty evidence; and RR 2.70, 95% CI 0.72 to 10.14; one trial, 19 participants; very low-certainty evidence; respectively) when compared to sham acupressure with or without sedation. Laser at P6 showed a difference in absence of gagging (odds ratio (OR) 86.33, 95% CI 29.41 to 253.45; one trial, 40 participants; very low-certainty evidence) and reduction in gagging (MD 1.80, 95% CI 1.53 to 2.07; one trial, 25 participants; very low-certainty evidence) during dental procedure when compared to dummy laser application. No noteworthy adverse effects were reported. For acupuncture at P6, the trial authors were unsure whether the reported adverse effects were due to participant anxiety or due to the intervention. None of the trials on acupressure or laser reported on this outcome. We did not find trials evaluating any other interventions used to manage gagging in people undergoing dental treatment.

    AUTHORS' CONCLUSIONS: We found very low-certainty evidence from four trials that was insufficient to conclude if there is any benefit of acupuncture, acupressure or laser at P6 point in reducing gagging and allowing successful completion of dental procedures. We did not find any evidence on any other interventions for managing the gag reflex during dental treatment. More well-designed and well-reported trials evaluating different interventions are needed.

  7. Poirot E, Skarbinski J, Sinclair D, Kachur SP, Slutsker L, Hwang J
    Cochrane Database Syst Rev, 2013 Dec 09;2013(12):CD008846.
    PMID: 24318836 DOI: 10.1002/14651858.CD008846.pub2
    BACKGROUND: Mass drug administration (MDA), defined as the empiric administration of a therapeutic antimalarial regimen to an entire population at the same time, has been a historic component of many malaria control and elimination programmes, but is not currently recommended. With renewed interest in MDA and its role in malaria elimination, this review aims to summarize the findings from existing research studies and program experiences of MDA strategies for reducing malaria burden and transmission.

    OBJECTIVES: To assess the impact of antimalarial MDA on population asexual parasitaemia prevalence, parasitaemia incidence, gametocytaemia prevalence, anaemia prevalence, mortality and MDA-associated adverse events.

    SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts, LILACS, reference lists, and recent conference proceedings.

    SELECTION CRITERIA: Cluster-randomized trials and non-randomized controlled studies comparing therapeutic MDA versus placebo or no MDA, and uncontrolled before-and-after studies comparing post-MDA to baseline data were selected. Studies administering intermittent preventive treatment (IPT) to sub-populations (for example, pregnant women, children or infants) were excluded.

    DATA COLLECTION AND ANALYSIS: Two authors independently reviewed studies for inclusion, extracted data and assessed risk of bias. Studies were stratified by study design and then subgrouped by endemicity, by co-administration of 8-aminoquinoline plus schizonticide drugs and by plasmodium species. The quality of evidence was assessed using the GRADE approach.

    MAIN RESULTS: Two cluster-randomized trials, eight non-randomized controlled studies and 22 uncontrolled before-and-after studies are included in this review. Twenty-two studies (29 comparisons) compared MDA to placebo or no intervention of which two comparisons were conducted in areas of low endemicity (≤5%), 12 in areas of moderate endemicity (6-39%) and 15 in areas of high endemicity (≥ 40%). Ten studies evaluated MDA plus other vector control measures. The studies used a wide variety of MDA regimens incorporating different drugs, dosages, timings and numbers of MDA rounds. Many of the studies are now more than 30 years old. Areas of low endemicity (≤5%)Within the first month post-MDA, a single uncontrolled before-and-after study conducted in 1955 on a small Taiwanese island reported a much lower prevalence of parasitaemia following a single course of chloroquine compared to baseline (1 study, very low quality evidence). This lower parasite prevalence was still present after more than 12 months (one study, very low quality evidence). In addition, one cluster-randomized trial evaluating MDA in a low endemic setting reported zero episodes of parasitaemia at baseline, and throughout five months of follow-up in both the control and intervention arms (one study, very low quality evidence). Areas of moderate endemicity (6-39%)Within the first month post-MDA, the prevalence of parasitaemia was much lower in three non-randomized controlled studies from Kenya and India in the 1950s (RR 0.03, 95% CI 0.01 to 0.08, three studies, moderate quality evidence), and in three uncontrolled before-and-after studies conducted between 1954 and 1961 (RR 0.29, 95% CI 0.17 to 0.48, three studies,low quality evidence).The longest follow-up in these settings was four to six months. At this time point, the prevalence of parasitaemia remained substantially lower than controls in the two non-randomized controlled studies (RR 0.18, 95% CI 0.10 to 0.33, two studies, low quality evidence). In contrast, the two uncontrolled before-and-after studies found mixed results: one found no difference and one found a substantially higher prevalence compared to baseline (not pooled, two studies, very low quality evidence). Areas of high endemicity (≥40%)Within the first month post-MDA, the single cluster-randomized trial from the Gambia in 1999 found no significant difference in parasite prevalence (one study, low quality evidence). However, prevalence was much lower during the MDA programmes in three non-randomized controlled studies conducted in the 1960s and 1970s (RR 0.17, 95% CI 0.11 to 0.27, three studies, moderate quality evidence), and within one month of MDA in four uncontrolled before-and-after studies (RR 0.37, 95% CI 0.28 to 0.49, four studies,low quality evidence).Four trials reported changes in prevalence beyond three months. In the Gambia, the single cluster-randomized trial found no difference at five months (one trial, moderate quality evidence). The three uncontrolled before-and-after studies had mixed findings with large studies from Palestine and Cambodia showing sustained reductions at four months and 12 months, respectively, and a small study from Malaysia showing no difference after four to six months of follow-up (three studies,low quality evidence). 8-aminoquinolines We found no studies directly comparing MDA regimens that included 8-aminoquinolines with regimens that did not. In a crude subgroup analysis with a limited number of studies, we were unable to detect any evidence of additional benefit of primaquine in moderate- and high-transmission settings. Plasmodium species In studies that reported species-specific outcomes, the same interventions resulted in a larger impact on Plasmodium falciparum compared to P. vivax.

    AUTHORS' CONCLUSIONS: MDA appears to reduce substantially the initial risk of malaria parasitaemia. However, few studies showed sustained impact beyond six months post-MDA, and those that did were conducted on small islands or in highland settings.To assess whether there is an impact of MDA on malaria transmission in the longer term requires more quasi experimental studies with the intention of elimination, especially in low- and moderate-transmission settings. These studies need to address any long-term outcomes, any potential barriers for community uptake, and contribution to the development of drug resistance.

  8. Karanth L, Kanagasabai S, Abas AB
    Cochrane Database Syst Rev, 2017 08 04;8:CD011059.
    PMID: 28776324 DOI: 10.1002/14651858.CD011059.pub3
    BACKGROUND: Bleeding disorders are uncommon but may pose significant bleeding complications during pregnancy, labour and following delivery for both the woman and the foetus. While many bleeding disorders in women tend to improve in pregnancy, thus decreasing the haemorrhagic risk to the mother at the time of delivery, some do not correct or return quite quickly to their pre-pregnancy levels in the postpartum period. Therefore, specific measures to prevent maternal bleeding and foetal complications during childbirth, are required. The safest method of delivery to reduce morbidity and mortality in these women is controversial. This is an update of a previously published review.

    OBJECTIVES: To assess the optimal mode of delivery in women with, or carriers of, bleeding disorders.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the Cochrane Pregnancy and Childbirth Group's Trials Register as well as trials registries and the reference lists of relevant articles and reviews.Date of last search of the Group's Trials Registers: 16 February 2017.

    SELECTION CRITERIA: Randomised controlled trials and all types of controlled clinical trials investigating the optimal mode of delivery in women with, or carriers of, any type of bleeding disorder during pregnancy were eligible for the review.

    DATA COLLECTION AND ANALYSIS: No trials matching the selection criteria were eligible for inclusion MAIN RESULTS: No results from randomised controlled trials were found.

    AUTHORS' CONCLUSIONS: The review did not identify any randomised controlled trials investigating the safest mode of delivery and associated maternal and foetal complications during delivery in women with, or carriers of, a bleeding disorder. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials, case studies) to decide upon the optimal mode of delivery to ensure the safety of both mother and foetus.Given the ethical considerations, the rarity of the disorders and the low incidence of both maternal and foetal complications, future randomised controlled trials to find the optimal mode of delivery in this population are unlikely to be carried out. Other high quality controlled studies (such as risk allocation designs, sequential design, and parallel cohort design) are needed to investigate the risks and benefits of natural vaginal and caesarean section in this population or extrapolation from other clinical conditions that incur a haemorrhagic risk to the baby, such as platelet alloimmunisation.

  9. Karanth L, Abas AB
    Cochrane Database Syst Rev, 2021 Dec 09;12(12):CD011059.
    PMID: 34881425 DOI: 10.1002/14651858.CD011059.pub4
    BACKGROUND: Bleeding disorders are uncommon but may pose significant bleeding complications during pregnancy, labour and following delivery for both the woman and the foetus. While many bleeding disorders in women tend to improve in pregnancy, thus decreasing the haemorrhagic risk to the mother at the time of delivery, some do not correct or return quite quickly to their pre-pregnancy levels in the postpartum period. Therefore, specific measures to prevent maternal bleeding and foetal complications during childbirth, are required. The safest method of delivery to reduce morbidity and mortality in these women is controversial. This is an update of a previously published review.

    OBJECTIVES: To assess the optimal mode of delivery in women with, or carriers of, bleeding disorders.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the Cochrane Pregnancy and Childbirth Group's Trials Register as well as trials registries and the reference lists of relevant articles and reviews. Date of last search of the Group's Trials Registers: 21 June 2021.

    SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled clinical trials investigating the optimal mode of delivery in women with, or carriers of, any type of bleeding disorder during pregnancy were eligible for the review.

    DATA COLLECTION AND ANALYSIS: No trials matching the selection criteria were eligible for inclusion.

    MAIN RESULTS: No trials matching the selection criteria were eligible for inclusion.

    AUTHORS' CONCLUSIONS: The review did not identify any randomised controlled trials investigating the safest mode of delivery and associated maternal and foetal complications during delivery in women with, or carriers of, a bleeding disorder. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials, case studies) to decide upon the optimal mode of delivery to ensure the safety of both mother and foetus. Given the ethical considerations, the rarity of the disorders and the low incidence of both maternal and foetal complications, future randomised controlled trials to find the optimal mode of delivery in this population are unlikely to be carried out. Other high quality controlled studies (such as risk allocation designs, sequential design, and parallel cohort design) are needed to investigate the risks and benefits of natural vaginal and caesarean section in this population or extrapolation from other clinical conditions that incur a haemorrhagic risk to the baby, such as platelet alloimmunisation.

  10. Karanth TK, Karanth VKLK, Ward BK, Woodworth BA, Karanth L
    Cochrane Database Syst Rev, 2022 Apr 07;4(4):CD012979.
    PMID: 35390177 DOI: 10.1002/14651858.CD012979.pub3
    BACKGROUND: Chronic rhinosinusitis frequently occurs in people with cystic fibrosis. Several medical interventions are available for treating chronic rhinosinusitis in people with cystic fibrosis; for example, different concentrations of nasal saline irrigations, topical or oral corticosteroids, antibiotics - including nebulized antibiotics - dornase alfa and modulators of the cystic fibrosis transmembrane conductance regulator (CFTR) (such as lumacaftor, ivacaftor or tezacaftor). However, the efficacy of these interventions is unclear. This is an update of a previously published review.

    OBJECTIVES: The objective of this review is to compare the effects of different medical interventions in people diagnosed with cystic fibrosis and chronic rhinosinusitis.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search of trials register: 09 September 2021. We also searched ongoing trials databases, other medical databases and the reference lists of relevant articles and reviews. Date of latest additional searches: 22 November 2021.

    SELECTION CRITERIA: Randomized and quasi-randomized trials of different medical interventions compared to each other or to no intervention or to placebo.

    DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials identified for potential inclusion in the review. We planned to conduct data collection and analysis in accordance with Cochrane methods and to independently rate the quality of the evidence for each outcome using the GRADE guidelines.

    MAIN RESULTS: We identified no trials that met the pre-defined inclusion criteria. The most recent searches identified 44 new references, none of which were eligible for inclusion in the current version of this review; 12 studies are listed as excluded and one as ongoing.

    AUTHORS' CONCLUSIONS: We identified no eligible trials assessing the medical interventions in people with cystic fibrosis and chronic rhinosinusitis. High-quality trials are needed which should assess the efficacy of different treatment options detailed above for managing chronic rhinosinusitis, preventing pulmonary exacerbations and improving quality of life in people with cystic fibrosis.

  11. Adler AJ, Martin N, Mariani J, Tajer CD, Owolabi OO, Free C, et al.
    Cochrane Database Syst Rev, 2017 Apr 29;4(4):CD011851.
    PMID: 28455948 DOI: 10.1002/14651858.CD011851.pub2
    BACKGROUND: Worldwide at least 100 million people are thought to have prevalent cardiovascular disease (CVD). This population has a five times greater chance of suffering a recurrent cardiovascular event than people without known CVD. Secondary CVD prevention is defined as action aimed to reduce the probability of recurrence of such events. Drug interventions have been shown to be cost-effective in reducing this risk and are recommended in international guidelines. However, adherence to recommended treatments remains sub-optimal. In order to influence non-adherence, there is a need to develop scalable and cost-effective behaviour-change interventions.

    OBJECTIVES: To assess the effects of mobile phone text messaging in patients with established arterial occlusive events on adherence to treatment, fatal and non-fatal cardiovascular events, and adverse effects.

    SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science on Web of Science on 7 November 2016, and two clinical trial registers on 12 November 2016. We contacted authors of included studies for missing information and searched reference lists of relevant papers. We applied no language or date restrictions.

    SELECTION CRITERIA: We included randomised trials with at least 50% of the participants with established arterial occlusive events. We included trials investigating interventions using short message service (SMS) or multimedia messaging service (MMS) with the aim to improve adherence to medication for the secondary prevention of cardiovascular events. Eligible comparators were no intervention or other modes of communication.

    DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. In addition, we attempted to contact all authors on how the SMS were developed.

    MAIN RESULTS: We included seven trials (reported in 13 reports) with 1310 participants randomised. Follow-up ranged from one month to 12 months. Due to heterogeneity in the methods, population and outcome measures, we were unable to conduct meta-analysis on these studies. All seven studies reported on adherence, but using different methods and scales. Six out of seven trials showed a beneficial effect of mobile phone text messaging for medication adherence. Dale 2015a, reported significantly greater medication adherence score in the intervention group (Mean Difference (MD) 0.58, 95% confidence interval (CI) 0.19 to 0.97; 123 participants randomised) at six months. Khonsari 2015 reported less adherence in the control group (Relative Risk (RR) 4.09, 95% CI 1.82 to 9.18; 62 participants randomised) at eight weeks. Pandey 2014 (34 participants randomised) assessed medication adherence through self-reported logs with 90% adherence in the intervention group compared to 70% in the control group at 12 months. Park 2014a (90 participants randomised) reported a greater increase of the medication adherence score in the control group, but also measured adherence with an event monitoring system for a number of medications with adherence levels ranging from 84.1% adherence to 86.2% in the intervention group and 79.7% to 85.7% in the control group at 30 days. Quilici 2013, reported reduced odds of non-adherence in the intervention group (Odds Ratio (OR) 0.43, 95% CI 0.22 to 0.86, 521 participants randomised) at 30 days. Fang 2016, reported that participants given SMS alone had reduced odds of being non-adherent compared to telephone reminders (OR 0.40 95% CI 0.18 to 0.63; 280 patients randomised). Kamal 2015 reported higher levels of adherence in the intervention arm (adjusted MD 0.54, 95% CI 0.22 to 0.85; 200 participants randomised). Khonsari 2015 was the only study to report fatal cardiovascular events and only reported two events, both in the control arm. No study reported on the other primary outcomes. No study reported repetitive thumb injury or road traffic crashes or other adverse events that were related to the intervention.Four authors replied to our questionnaire on SMS development. No study reported examining causes of non-adherence or provided SMS tailored to individual patient characteristics.The included studies were small, heterogeneous and included participants recruited directly after acute events. All studies were assessed as having high risk of bias across at least one domain. Most of the studies came from high-income countries, with two studies conducted in an upper middle-income country (China, Malaysia), and one study from a lower middle-income country (Pakistan). The quality of the evidence was found to be very low. There was no obvious conflicts of interest from authors, although only two declared their funding.

    AUTHORS' CONCLUSIONS: While the results of this systematic review are promising, there is insufficient evidence to draw conclusions on the effectiveness of text message-based interventions for adherence to medications for secondary prevention of CVD. Sufficiently powered, high-quality randomised trials are needed, particularly in low- and middle-income countries.

  12. Ooi CP, Yassin Z, Hamid TA
    PMID: 20166099 DOI: 10.1002/14651858.CD007845.pub2
    Background: Momordica charantia is not only a nutritious vegetable, but is also used in traditional medical practices to treat type 2 diabetes mellitus. Experimental studies with animals and humans suggested that the vegetable has a possible role in glycaemic control.

    Objectives: To assess the effects of mormodica charantia for type 2 diabetes mellitus.

    Search strategy: Several electronic databases were searched, among these The Cochrane Library (issue 4, 2009), MEDLINE, EMBASE, CINAHL, SIGLE and LILACS (all up to November 2009), combined with handsearches. No language restriction was used.

    Selection criteria: Randomized controlled trials that compared momordica charantia with a placebo or a control intervention with or without pharmacological or non-pharmacological interventions were included.

    Data collection and analysis: Two authors independently extracted the data. Risk of bias of trials was evaluated using the parameters of randomization, allocation concealment, blinding, completeness of outcome data, selective reporting and other potential sources of bias. A meta-analysis was not performed given the quality of data and the variability of preparations of momordica charantia used in interventions (no similar preparation was tested twice).

    Main results: Three randomised controlled trials with up to three months duration and investigating 350 participants met the inclusion criteria. Risk of bias of these trials (only one study was published as a full peer-reviewed publication) was generally high. Two RCTs compared the effect of preparations from different parts of the momordica charantia plants and placebo on the glycemic control in type 2 diabetes mellitus. There was no statistically significant difference compared to placebo. The effects of preparation from the leaves of the plant and glibenclamide were comparable in the third trial. No serious adverse effects were reported in all the trials. There were no documentations of death from any cause, morbidity, (health-related) quality of life and costs.

    Authors' conclusions: There is insufficient evidence to recommend momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice.
  13. Ooi CP, Yassin Z, Hamid TA
    PMID: 22895968 DOI: 10.1002/14651858.CD007845.pub3
    BACKGROUND: Momordica charantia (bitter gourd) is not only a nutritious vegetable but it is also used in traditional medical practices to treat type 2 diabetes mellitus. Experimental studies with animals and humans suggested that the vegetable has a possible role in glycaemic control.

    OBJECTIVES: To assess the effects of mormodica charantia for type 2 diabetes mellitus.

    SEARCH METHODS: Several electronic databases were searched, among these were The Cochrane Library (Issue 1, 2012), MEDLINE, EMBASE, CINAHL, SIGLE and LILACS (all up to February 2012), combined with handsearches. No language restriction was used.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared momordica charantia with placebo or a control intervention, with or without pharmacological or non-pharmacological interventions.

    DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. Risk of bias of the trials was evaluated using the parameters of randomisation, allocation concealment, blinding, completeness of outcome data, selective reporting and other potential sources of bias. A meta-analysis was not performed given the quality of data and the variability of preparations of momordica charantia used in the interventions (no similar preparation was tested twice).

    MAIN RESULTS: Four randomised controlled trials with up to three months duration and investigating 479 participants met the inclusion criteria. Risk of bias of these trials (only two studies were published as a full peer-reviewed publication) was generally high. Two RCTs compared the effects of preparations from different parts of the momordica charantia plant with placebo on glycaemic control in type 2 diabetes mellitus. There was no statistically significant difference in the glycaemic control with momordica charantia preparations compared to placebo. When momordica charantia was compared to metformin or glibenclamide, there was also no significant change in reliable parameters of glycaemic control. No serious adverse effects were reported in any trial. No trial investigated death from any cause, morbidity, health-related quality of life or costs.

    AUTHORS' CONCLUSIONS: There is insufficient evidence on the effects of momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice.

  14. Kokavec J, Wu Z, Sherwin JC, Ang AJ, Ang GS
    Cochrane Database Syst Rev, 2017 Jun 01;6:CD011676.
    PMID: 28570745 DOI: 10.1002/14651858.CD011676.pub2
    BACKGROUND: The vitreous is the clear jelly of the eye and contains fine strands of proteins. Throughout life the composition of this vitreous changes, which causes the protein strands in it to bundle together and scatter light before it reaches the retina. Individuals perceive the shadows cast by these protein bundles as 'floaters'. Some people are so bothered by floaters that treatment is required to control their symptoms. Two major interventions for floaters include Nd:YAG laser vitreolysis and vitrectomy. Nd:YAG laser vitreolysis involves using laser energy to fragment the vitreous opacities via a non-invasive approach. Vitrectomy involves the surgical replacement of the patient's vitreous (including the symptomatic vitreous floaters) with an inert and translucent balanced salt solution, through small openings in the pars plana.

    OBJECTIVES: To compare the effectiveness and safety of Nd:YAG laser vitreolysis to pars plana vitrectomy for symptomatic vitreous floaters.

    SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), MEDLINE Ovid (1946 to 17 January 2017), Embase Ovid (1947 to 17 January 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 17 January 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 17 January 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 17 January 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 17 January 2017. We did not use any date or language restrictions in the electronic searches for trials. We also searched conference proceedings to identify additional studies.

    SELECTION CRITERIA: We included only randomised controlled trials (RCTs) that compared Nd:YAG laser vitreolysis to pars plana vitrectomy for treatment of symptomatic floaters.

    DATA COLLECTION AND ANALYSIS: We planned to use methods recommended by Cochrane. The primary outcome we planned to measure was change in vision-related quality of life from baseline to 12 months, as determined by a vision-related quality of life questionnaire. The secondary outcomes we planned to measure were best corrected logMAR or Snellen visual acuity at 12 months for the treated eye(s) and costs. Adverse outcomes we planned to record were the occurrence of sight-threatening complications by 12 months (asymptomatic retinal tears, symptomatic retinal tears, retinal detachment, cataract formation, and endophthalmitis).

    MAIN RESULTS: No studies met the inclusion criteria of this review.

    AUTHORS' CONCLUSIONS: There are currently no RCTs that compare Nd:YAG laser vitreolysis with pars plana vitrectomy for the treatment of symptomatic floaters. Properly designed RCTs are needed to evaluate the treatment outcomes from the interventions described. We recommend future studies randomise participants to either a Nd:YAG laser vitreolysis group or a vitrectomy group, with participants in each group assigned to either receive treatment or a sham intervention. Future studies should follow participants at six months and 12 months after the intervention. Also they should use best corrected visual acuity (BCVA) using an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart read at 4 metres, vision-related quality of life (VRQOL), and adverse outcomes as the outcome measures of the trial.

  15. Foong SC, Tan ML, Foong WC, Marasco LA, Ho JJ, Ong JH
    Cochrane Database Syst Rev, 2020 May 18;5(5):CD011505.
    PMID: 32421208 DOI: 10.1002/14651858.CD011505.pub2
    BACKGROUND: Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use.

    OBJECTIVES: To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs.

    SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019).

    SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials.

    DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification.

    MAIN RESULTS: Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I2 = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I2 = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome.

    AUTHORS' CONCLUSIONS: Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used.

  16. Jaafar SH, Jahanfar S, Angolkar M, Ho JJ
    PMID: 21412899 DOI: 10.1002/14651858.CD007202.pub2
    To successfully initiate and maintain breastfeeding for a longer duration, the World Health Organization's Ten Steps to Successful Breastfeeding recommends total avoidance of artificial teats or pacifiers for breastfeeding infants. Offering the pacifier instead of the breast to calm the infant may lead to less frequent episodes of breastfeeding and as a consequence may reduce breast milk production and shorten duration of breastfeeding; however, this remains unclear.
  17. Tan ML, Ho JJ, Teh KH
    Cochrane Database Syst Rev, 2016 Sep 28;9:CD009398.
    PMID: 27678554 DOI: 10.1002/14651858.CD009398.pub3
    BACKGROUND: About 5% of school children have a specific learning disorder, defined as unexpected failure to acquire adequate abilities in reading, writing or mathematics that is not a result of reduced intellectual ability, inadequate teaching or social deprivation. Of these events, 80% are reading disorders. Polyunsaturated fatty acids (PUFAs), in particular, omega-3 and omega-6 fatty acids, which normally are abundant in the brain and in the retina, are important for learning. Some children with specific learning disorders have been found to be deficient in these PUFAs, and it is argued that supplementation of PUFAs may help these children improve their learning abilities.

    OBJECTIVES: 1. To assess effects on learning outcomes of supplementation of polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.2. To determine whether adverse effects of supplementation of PUFAs are reported in these children.

    SEARCH METHODS: In November 2015, we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, 10 other databases and two trials registers. We also searched the reference lists of relevant articles.

    SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing PUFAs with placebo or no treatment in children younger than 18 years with specific learning disabilities, as diagnosed in accordance with the fifth (or earlier) edition of theDiagnostic and Statistical Manual of Mental Disorders (DSM-5), or the 10th (or earlier) revision of the International Classification of Diseases (ICD-10) or equivalent criteria. We included children with coexisting developmental disorders such as attention deficit hyperactivity disorder (ADHD) or autism.

    DATA COLLECTION AND ANALYSIS: Two review authors (MLT and KHT) independently screened the titles and abstracts of articles identified by the search and eliminated all studies that did not meet the inclusion criteria. We contacted study authors to ask for missing information and clarification, when needed. We used the GRADE approach to assess the quality of evidence.

    MAIN RESULTS: Two small studies involving 116 children, mainly boys between 10 and 18 years of age, met the inclusion criteria. One study was conducted in a school setting, the other at a specialised clinic. Both studies used three months of a combination of omega-3 and omega-6 supplements as the intervention compared with placebo. Although both studies had generally low risk of bias, we judged the risk of reporting bias as unclear in one study, and as high in the other study. In addition, one of the studies was funded by industry and reported active company involvement in the study.None of the studies reported data on the primary outcomes of reading, writing, spelling and mathematics scores, as assessed by standardised tests.Evidence of low quality indicates that supplementation of PUFAs did not increase the risk of gastrointestinal disturbances (risk ratio 1.43, 95% confidence interval 0.25 to 8.15; two studies, 116 children). Investigators reported no other adverse effects.Both studies reported attention deficit hyperactivity disorder (ADHD)-related behaviour outcomes. We were unable to combine the results in a meta-analysis because one study reported findings as a continuous outcome, and the other as a dichotomous outcome. No other secondary outcomes were reported.We excluded one study because it used a cointervention (carnosine), and five other studies because they did not provide a robust diagnosis of a specific learning disorder. We identified one ongoing study and found three studies awaiting classification.

    AUTHORS' CONCLUSIONS: Evidence is insufficient to permit any conclusions about the effect of PUFAs on the learning abilities of children with specific learning disorders. Well-designed RCTs with clearly defined populations of children with specific learning disorders who have been diagnosed by standardised diagnostic criteria are needed.

  18. Yaacob M, Worthington HV, Deacon SA, Deery C, Walmsley AD, Robinson PG, et al.
    PMID: 24934383 DOI: 10.1002/14651858.CD002281.pub3
    BACKGROUND: Removing dental plaque may play a key role maintaining oral health. There is conflicting evidence for the relative merits of manual and powered toothbrushing in achieving this. This is an update of a Cochrane review first published in 2003, and previously updated in 2005.

    OBJECTIVES: To compare manual and powered toothbrushes in everyday use, by people of any age, in relation to the removal of plaque, the health of the gingivae, staining and calculus, dependability, adverse effects and cost.

    SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 23 January 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE via OVID (1946 to 23 January 2014), EMBASE via OVID (1980 to 23 January 2014) and CINAHL via EBSCO (1980 to 23 January 2014). We searched the US National Institutes of Health Trials Register and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.

    SELECTION CRITERIA: Randomised controlled trials of at least four weeks of unsupervised powered toothbrushing versus manual toothbrushing for oral health in children and adults.

    DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. Random-effects models were used provided there were four or more studies included in the meta-analysis, otherwise fixed-effect models were used. Data were classed as short term (one to three months) and long term (greater than three months).

    MAIN RESULTS: Fifty-six trials met the inclusion criteria; 51 trials involving 4624 participants provided data for meta-analysis. Five trials were at low risk of bias, five at high and 46 at unclear risk of bias.There is moderate quality evidence that powered toothbrushes provide a statistically significant benefit compared with manual toothbrushes with regard to the reduction of plaque in both the short term (standardised mean difference (SMD) -0.50 (95% confidence interval (CI) -0.70 to -0.31); 40 trials, n = 2871) and long term (SMD -0.47 (95% CI -0.82 to -0.11; 14 trials, n = 978). These results correspond to an 11% reduction in plaque for the Quigley Hein index (Turesky) in the short term and 21% reduction long term. Both meta-analyses showed high levels of heterogeneity (I(2) = 83% and 86% respectively) that was not explained by the different powered toothbrush type subgroups.With regard to gingivitis, there is moderate quality evidence that powered toothbrushes again provide a statistically significant benefit when compared with manual toothbrushes both in the short term (SMD -0.43 (95% CI -0.60 to -0.25); 44 trials, n = 3345) and long term (SMD -0.21 (95% CI -0.31 to -0.12); 16 trials, n = 1645). This corresponds to a 6% and 11% reduction in gingivitis for the Löe and Silness index respectively. Both meta-analyses showed high levels of heterogeneity (I(2) = 82% and 51% respectively) that was not explained by the different powered toothbrush type subgroups.The number of trials for each type of powered toothbrush varied: side to side (10 trials), counter oscillation (five trials), rotation oscillation (27 trials), circular (two trials), ultrasonic (seven trials), ionic (four trials) and unknown (five trials). The greatest body of evidence was for rotation oscillation brushes which demonstrated a statistically significant reduction in plaque and gingivitis at both time points.

    AUTHORS' CONCLUSIONS: Powered toothbrushes reduce plaque and gingivitis more than manual toothbrushing in the short and long term. The clinical importance of these findings remains unclear. Observation of methodological guidelines and greater standardisation of design would benefit both future trials and meta-analyses.Cost, reliability and side effects were inconsistently reported. Any reported side effects were localised and only temporary.

  19. Hussein N, Weng SF, Kai J, Kleijnen J, Qureshi N
    PMID: 26264938 DOI: 10.1002/14651858.CD010849.pub2
    BACKGROUND: Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting.

    OBJECTIVES: To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 25 June 2015.Date of latest search of all other sources: 10 December 2014.

    SELECTION CRITERIA: Any randomised or quasi-randomised control trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care.

    DATA COLLECTION AND ANALYSIS: We identified 19 papers, describing 13 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found.

    MAIN RESULTS: No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found.

    AUTHORS' CONCLUSIONS: As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies.Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment.

  20. Hussein N, Weng SF, Kai J, Kleijnen J, Qureshi N
    Cochrane Database Syst Rev, 2018 03 14;3:CD010849.
    PMID: 29537064 DOI: 10.1002/14651858.CD010849.pub3
    BACKGROUND: Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. This is an update of a previously published review.

    OBJECTIVES: To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 20 June 2017.Date of latest search of all other sources: 16 November 2017.

    SELECTION CRITERIA: Any randomised or quasi-randomised controlled trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care.

    DATA COLLECTION AND ANALYSIS: We identified 25 papers, describing 16 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found.

    MAIN RESULTS: No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were included. One ongoing trial has been identified which may potentially eligible for inclusion once completed.

    AUTHORS' CONCLUSIONS: As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies.Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment.

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